Use of macrocyclic picolinamides as fungicides

ABSTRACT

The invention relates to macrocyclic picolinamides of Formula I and their use as fungicides.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication Ser. Nos. 61/920,962 and 61/920,966, each filed Dec. 26,2013, the disclosures of which are hereby incorporated by reference intheir entireties.

BACKGROUND & SUMMARY

Fungicides are compounds, of natural or synthetic origin, which act toprotect and/or cure plants against damage caused by agriculturallyrelevant fungi. Generally, no single fungicide is useful in allsituations. Consequently, research is ongoing to produce fungicides thatmay have better performance, are easier to use, and cost less.

The present disclosure relates to macrocyclic picolinamides and theiruse as fungicides. The compounds of the present disclosure may offerprotection against ascomycetes, basidiomycetes, deuteromycetes andoomycetes.

One embodiment of the present disclosure may include compounds ofFormula I:

X is hydrogen or C(O)R₃;

Y is hydrogen, C(O)R₃, or Q;

Q is

R₁ is hydrogen, alkyl, acyl, alkenyl, aryl, or alkoxy, each optionallysubstituted with 0, 1 or multiple R₆;

R₂ is hydrogen, alkyl, acyl, alkenyl, aryl, or —Si(R₅)₃, each optionallysubstituted with 0, 1 or multiple R₆;

R₃ alkoxy or benzyloxy, each optionally substituted with 0, 1, ormultiple R₆;

R₄ is hydrogen, —C(O)R₅, or —CH₂OC(O)R₅;

R₅ is alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, ormultiple R₆;

R₆ is hydrogen, alkyl, aryl, halo, acyl, alkenyl, alkoxy, heteroaryl,heterocyclyl, or thioalkyl, each optionally substituted with 0, 1, ormultiple R₇; and

R₇ is hydrogen, alkyl, aryl, or halo.

Another embodiment of the present disclosure may include a fungicidalcomposition for the control or prevention of fungal attack comprisingthe compounds described above and a phytologically acceptable carriermaterial.

Yet another embodiment of the present disclosure may include a methodfor the control or prevention of fungal attack on a plant, the methodincluding the steps of applying a fungicidally effective amount of oneor more of the compounds described above to at least one of the fungus,the plant, and an area adjacent to the plant.

It will be understood by the those skilled in the art that the followingterms may include generic “R”-groups within their definitions, e.g.,“the term alkoxy refers to an —OR substituent”. It is also understoodthat within the definitions for the following terms, these “R” groupsare included for illustration purposes and should not be construed aslimiting or being limited by substitutions about Formula I.

The term “alkyl” refers to a branched, unbranched, or saturated cycliccarbon chain, including, but not limited to, methyl, ethyl, propyl,butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl and the like. In some exemplaryembodiments, the term “alkyl” refers to a branched, unbranched, orsaturated cyclic carbon chain, including containing from 1 to 12 carbonatoms, from 1 to 6 carbons, or from 1 to 4 carbons.

The term “alkenyl” refers to a branched, unbranched or cyclic carbonchain containing one or more double bonds including, but not limited to,ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl,cyclopentenyl, cyclohexenyl, and the like. In some exemplaryembodiments, the term “alkenyl” refers to a branched, unbranched, orsaturated cyclic carbon chain, including containing from 1 to 12 carbonatoms, from 1 to 6 carbons, or from 1 to 4 carbons.

The term “alkynyl” refers to a branched or unbranched carbon chaincontaining one or more triple bonds including, but not limited to,propynyl, butynyl and the like. In some exemplary embodiments, the term“alkynyl” refers to a branched, unbranched, or saturated cyclic carbonchain, including containing from 1 to 12 carbon atoms, from 1 to 6carbons, or from 1 to 4 carbons.

The term “aryl” refers to any aromatic, mono- or bi-cyclic ring,containing 0 heteroatoms.

The term “heterocycle” refers to any aromatic or non-aromatic ring,mono- or bi-cyclic, containing one or more heteroatoms. In someexemplary embodiments, the one or more heteroatoms are independentlyselected from nitrogen, oxygen, phosphorous, and sulfur.

The term “alkoxy” refers to an —OR substituent.

The term “cyano” refers to a —C≡N substituent.

The term “hydroxyl” refers to an —OH substituent.

The term “amino” refers to a —NH₂ substituent.

The term “arylalkoxy” refers to —O(CH₂)_(n)—Ar where n is an integerselected from the list 1, 2, 3, 4, 5, or 6.

The term “haloalkoxy” refers to an —OR—X substituent, wherein X is Cl,F, Br, or I, or any combination thereof.

The term “haloalkyl” refers to an alkyl, which is substituted with Cl,F, I, or Br or any combination thereof.

The term “halogen” or “halo” refers to one or more halogen atoms,defined as F, Cl, Br, and I.

The term “nitro” refers to a —NO₂ substituent.

The term thioalkyl refers to an —SR substituent.

Throughout the disclosure, reference to the compounds of Formula I isread as also including diastereomers, enantiomers, and mixtures thereof.In another embodiment, Formula (I) is read as also including salts orhydrates thereof. Exemplary salts include, but are not limited to:hydrochloride, hydrobromide, and hydroiodide.

It is also understood by those skilled in the art that additionalsubstitution is allowable, unless otherwise noted, as long as the rulesof chemical bonding and strain energy are satisfied and the productstill exhibits fungicidal activity.

Another embodiment of the present disclosure is a use of a compound ofFormula I, for protection of a plant against attack by a phytopathogenicorganism or the treatment of a plant infested by a phytopathogenicorganism, comprising the application of a compound of Formula I, or acomposition comprising the compound to soil, a plant, a part of a plant,foliage, and/or roots.

Additionally, another embodiment of the present disclosure is acomposition useful for protecting a plant against attack by aphytopathogenic organism and/or treatment of a plant infested by aphytopathogenic organism comprising a compound of Formula I and aphytologically acceptable carrier material.

In one exemplary embodiment, a composition for the control of a fungalpathogen is provided. The composition at least one of the compounds ofFormula 1:

-   -   wherein    -   X is hydrogen or C(O)R₃;    -   Y is hydrogen, C(O)R₃, or Q;    -   Q is

-   -   R₁ is hydrogen, alkyl, alkenyl, aryl, alkoxy, or acyl, each        optionally substituted with 0, 1 or multiple R₆;    -   R₂ is hydrogen, alkyl, acyl, aryl, alkenyl, or —Si(R₅)₃, each        optionally substituted with 0, 1 or multiple R₆;    -   R₃ is alkoxy or benzyloxy, each optionally substituted with 0,        1, or multiple R₆;    -   R₄ is hydrogen, —C(O)R₅, or —CH₂OC(O)R₅;    -   R₅ is alkyl, alkoxy, or aryl, each optionally substituted with        0, 1, or multiple R₆;    -   R₆ is hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy,        heteroaryl, heterocyclyl, or thioalkyl, each optionally        substituted with 0, 1, or multiple R₇; and    -   R₇ is hydrogen, alkyl, aryl, or halo.

In a one more particular embodiment, X is hydrogen and Y is Q. Inanother more particular embodiment of any of the above embodiments, R₄is hydrogen. In another more particular embodiment of any of the aboveembodiments, R₁ is chosen from alkyl and aryl, each optionallysubstituted with 0, 1 or multiple R₆. In another more particularembodiment of any of the above embodiments, R₂ is chosen from alkyl,aryl, and acyl, each optionally substituted with 0, 1 or multiple R₆. Inanother more particular embodiment of any of the above embodiments, R₁is chosen from alkyl and aryl, each optionally substituted with 0, 1 ormultiple R₆, and R₂ is chosen from alkyl, aryl, and acyl, eachoptionally substituted with 0, 1 or multiple R₆. In another moreparticular embodiment of any of the above embodiments, R₄ is —C(O)R₅ or—CH₂OC(O)R₅. In another more particular embodiment of any of the aboveembodiments, R₅ is chosen from alkyl and alkoxy, each optionallysubstituted with 0, 1, or multiple R₆. In another more particularembodiment of any of the above embodiments, R₁ is chosen from alkyl andaryl, each optionally substituted with 0, 1 or multiple R₆. In anothermore particular embodiment of any of the above embodiments, R₂ is chosenfrom alkyl, aryl, and acyl, each optionally substituted with 0, 1 ormultiple R₆. In another more particular embodiment of any of the aboveembodiments, R₁ is chosen from alkyl and aryl, each optionallysubstituted with 0, 1 or multiple R₆, and R₂ is chosen from alkyl, aryl,and acyl, each optionally substituted with 0, 1 or multiple R₆. Inanother more particular embodiment of any of the above embodiments, R₅is chosen from —CH₃ and —CH₂OCH₂CH₃.

In another more particular embodiment of any of the above embodiments,the composition further includes a phytologically acceptable carriermaterial.

In another more particular embodiment of any of the above embodiments,the composition further includes another pesticide. Exemplary pesticidesinclude fungicides, insecticides, nematocides, miticides,arthropodicides, bactericides and combinations thereof.

In another more particular embodiment of any of the above embodiments,the fungal pathogen is one of Leaf Blotch of Wheat (Mycosphaerellagraminicola; anamorph: Septoria tritici), Wheat Brown Rust (Pucciniatriticina), Stripe Rust (Puccinia striiformis), Scab of Apple (Venturiainaequalis), Blister Smut of Maize (Ustilago maydis), Powdery Mildew ofGrapevine (Uncinula necator), Barley scald (Rhynchosporium secalis),Blast of Rice (Magnaporthe grisea), Rust of Soybean (Phakopsorapachyrhizi), Glume Blotch of Wheat (Leptosphaeria nodorum), PowderyMildew of Wheat (Blumeria graminis f sp. tritici), Powdery Mildew ofBarley (Blumeria graminis f sp. hordei), Powdery Mildew of Cucurbits(Erysiphe cichoracearum), Anthracnose of Cucurbits (Glomerellalagenarium), Leaf Spot of Beet (Cercospora beticola), Early Blight ofTomato (Alternaria solani), and Net Blotch of Barley (Pyrenophorateres). In an even more particular embodiment, the fungal pathogen isone of Leaf Blotch of Wheat (Septoria tritici), Wheat Brown Rust(Puccinia triticina), and Rust of Soybean (Phakopsora pachyrhizi).

In another embodiment, a method for the control and prevention of fungalattack on a plant is provided. The method includes applying afungicidally effective amount of at least one of any of the abovecompositions to at least one of the plant, an area adjacent to theplant, soil adapted to support growth of the plant, a root of the plant,and foliage of the plant.

DETAILED DESCRIPTION

The compounds of the present disclosure may be applied by any of avariety of known techniques, either as the compounds or as formulationscomprising the compounds. For example, the compounds may be applied tothe roots or foliage of plants for the control of various fungi, withoutdamaging the commercial value of the plants. The materials may beapplied in the form of any of the generally used formulation types, forexample, as solutions, dusts, wettable powders, flowable concentrate, oremulsifiable concentrates.

Preferably, the compounds of the present disclosure are applied in theform of a formulation, comprising one or more of the compounds ofFormula I with a phytologically acceptable carrier. Concentratedformulations may be dispersed in water, or other liquids, forapplication, or formulations may be dust-like or granular, which maythen be applied without further treatment. The formulations can beprepared according to procedures that are conventional in theagricultural chemical art.

The present disclosure contemplates all vehicles by which one or more ofthe compounds may be formulated for delivery and use as a fungicide.Typically, formulations are applied as aqueous suspensions or emulsions.Such suspensions or emulsions may be produced from water-soluble,water-suspendable, or emulsifiable formulations which are solids,usually known as wettable powders; or liquids, usually known asemulsifiable concentrates, aqueous suspensions, or suspensionconcentrates. As will be readily appreciated, any material to whichthese compounds may be added may be used, provided it yields the desiredutility without significant interference with the activity of thesecompounds as antifungal agents.

Wettable powders, which may be compacted to form water-dispersiblegranules, comprise an intimate mixture of one or more of the compoundsof Formula I, an inert carrier and surfactants. The concentration of thecompound in the wettable powder may be from about 10 percent to about 90percent by weight based on the total weight of the wettable powder, morepreferably about 25 weight percent to about 75 weight percent. In thepreparation of wettable powder formulations, the compounds may becompounded with any finely divided solid, such as prophyllite, talc,chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein,gluten, montmorillonite clays, diatomaceous earths, purified silicatesor the like. In such operations, the finely divided carrier andsurfactants are typically blended with the compound(s) and milled.

Emulsifiable concentrates of the compounds of Formula I may comprise aconvenient concentration, such as from about 1 weight percent to about50 weight percent of the compound, in a suitable liquid, based on thetotal weight of the concentrate. The compounds may be dissolved in aninert carrier, which is either a water-miscible solvent or a mixture ofwater-immiscible organic solvents, and emulsifiers. The concentrates maybe diluted with water and oil to form spray mixtures in the form ofoil-in-water emulsions. Useful organic solvents include aromatics,especially the high-boiling naphthalenic and olefinic portions ofpetroleum such as heavy aromatic naphtha. Other organic solvents mayalso be used, for example, terpenic solvents, including rosinderivatives, aliphatic ketones, such as cyclohexanone, and complexalcohols, such as 2-ethoxyethanol.

Emulsifiers which may be advantageously employed herein may be readilydetermined by those skilled in the art and include various nonionic,anionic, cationic and amphoteric emulsifiers, or a blend of two or moreemulsifiers. Examples of nonionic emulsifiers useful in preparing theemulsifiable concentrates include the polyalkylene glycol ethers andcondensation products of alkyl and aryl phenols, aliphatic alcohols,aliphatic amines or fatty acids with ethylene oxide, propylene oxidessuch as the ethoxylated alkyl phenols and carboxylic esters solubilizedwith the polyol or polyoxyalkylene. Cationic emulsifiers includequaternary ammonium compounds and fatty amine salts. Anionic emulsifiersinclude the oil-soluble salts (e.g., calcium) of alkylaryl sulphonicacids, oil-soluble salts or sulfated polyglycol ethers and appropriatesalts of phosphated polyglycol ether.

Representative organic liquids which may be employed in preparing theemulsifiable concentrates of the compounds of the present disclosure arethe aromatic liquids such as xylene, propyl benzene fractions; or mixednaphthalene fractions, mineral oils, substituted aromatic organicliquids such as dioctyl phthalate; kerosene; dialkyl amides of variousfatty acids, particularly the dimethyl amides of fatty glycols andglycol derivatives such as the n-butyl ether, ethyl ether or methylether of diethylene glycol, the methyl ether of triethylene glycol,petroleum fractions or hydrocarbons such as mineral oil, aromaticsolvents, paraffinic oils, and the like; vegetable oils such as soy beanoil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconutoil, corn oil, cotton seed oil, linseed oil, palm oil, peanut oil,safflower oil, sesame oil, tung oil and the like; esters of the abovevegetable oils; and the like. Mixtures of two or more organic liquidsmay also be employed in the preparation of the emulsifiable concentrate.Organic liquids include xylene, and propyl benzene fractions, withxylene being most preferred in some cases. Surface-active dispersingagents are typically employed in liquid formulations and in an amount offrom 0.1 to 20 percent by weight based on the combined weight of thedispersing agent with one or more of the compounds. The formulations canalso contain other compatible additives, for example, plant growthregulators and other biologically active compounds used in agriculture.

Aqueous suspensions comprise suspensions of one or more water-insolublecompounds of Formula I, dispersed in an aqueous vehicle at aconcentration in the range from about 1 to about 50 weight percent,based on the total weight of the aqueous suspension. Suspensions areprepared by finely grinding one or more of the compounds, and vigorouslymixing the ground material into a vehicle comprised of water andsurfactants chosen from the same types discussed above. Othercomponents, such as inorganic salts and synthetic or natural gums, mayalso be added to increase the density and viscosity of the aqueousvehicle.

The compounds of Formula I can also be applied as granular formulations,which are particularly useful for applications to the soil. Granularformulations generally contain from about 0.5 to about 10 weightpercent, based on the total weight of the granular formulation of thecompound(s), dispersed in an inert carrier which consists entirely or inlarge part of coarsely divided inert material such as attapulgite,bentonite, diatomite, clay or a similar inexpensive substance. Suchformulations are usually prepared by dissolving the compounds in asuitable solvent and applying it to a granular carrier which has beenpreformed to the appropriate particle size, in the range of from about0.5 to about 3 mm. A suitable solvent is a solvent in which the compoundis substantially or completely soluble. Such formulations may also beprepared by making a dough or paste of the carrier and the compound andsolvent, and crushing and drying to obtain the desired granularparticle.

Dusts containing the compounds of Formula I may be prepared byintimately mixing one or more of the compounds in powdered form with asuitable dusty agricultural carrier, such as, for example, kaolin clay,ground volcanic rock, and the like. Dusts can suitably contain fromabout 1 to about 10 weight percent of the compounds, based on the totalweight of the dust.

The formulations may additionally contain adjuvant surfactants toenhance deposition, wetting and penetration of the compounds onto thetarget crop and organism. These adjuvant surfactants may optionally beemployed as a component of the formulation or as a tank mix. The amountof adjuvant surfactant will typically vary from 0.01 to 1.0 percent byvolume, based on a spray-volume of water, preferably 0.05 to 0.5 volumepercent. Suitable adjuvant surfactants include, but are not limited toethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols,salts of the esters or sulphosuccinic acids, ethoxylatedorganosilicones, ethoxylated fatty amines, blends of surfactants withmineral or vegetable oils, crop oil concentrate (mineral oil(85%)+emulsifiers (15%)); nonylphenol ethoxylate;benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleumhydrocarbon, alkyl esters, organic acid, and anionic surfactant; C₉-C₁₁alkylpolyglycoside; phosphated alcohol ethoxylate; natural primaryalcohol (C₁₂-C₁₆) ethoxylate; di-sec-butylphenol EO-PO block copolymer;polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium nitrate;emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate(8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99. Theformulations may also include oil-in-water emulsions such as thosedisclosed in U.S. patent application Ser. No. 11/495,228, the disclosureof which is expressly incorporated by reference herein.

The formulations may optionally include combinations that contain otherpesticidal compounds. Such additional pesticidal compounds may befungicides, insecticides, herbicides, nematocides, miticides,arthropodicides, bactericides or combinations thereof that arecompatible with the compounds of the present disclosure in the mediumselected for application, and not antagonistic to the activity of thepresent compounds. Accordingly, in such embodiments, the otherpesticidal compound is employed as a supplemental toxicant for the sameor for a different pesticidal use. The compounds of Formula I and thepesticidal compound in the combination can generally be present in aweight ratio of from 1:100 to 100:1.

The compounds of the present disclosure may also be combined with otherfungicides to form fungicidal mixtures and synergistic mixtures thereof.The fungicidal compounds of the present disclosure are often applied inconjunction with one or more other fungicides to control a wider varietyof undesirable diseases. When used in conjunction with otherfungicide(s), the presently claimed compounds may be formulated with theother fungicide(s), tank-mixed with the other fungicide(s) or appliedsequentially with the other fungicide(s). Such other fungicides mayinclude 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol,8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin,Ampelomyces quisqualis, azaconazole, azoxystrobin, Bacillus subtilis,Bacillus subtilis strain QST713, benalaxyl, benomyl,benthiavalicarb-isopropyl, benzovindiflupyr,benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl,bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeauxmixture, boscalid, bromuconazole, bupirimate, calcium polysulfide,captafol, captan, carbendazim, carboxin, carpropamid, carvone,chlazafenone, chloroneb, chlorothalonil, chlozolinate, Coniothyriumminitans, copper hydroxide, copper octanoate, copper oxychloride, coppersulfate, copper sulfate (tribasic), cuprous oxide, cyazofamid,cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb,diammonium ethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen,diclocymet, diclomezine, dichloran, diethofencarb, difenoconazole,difenzoquat ion, diflumetorim, dimethomorph, dimoxystrobin,diniconazole, diniconazole-M, dinobuton, dinocap, diphenylamine,dithianon, dodemorph, dodemorph acetate, dodine, dodine free base,edifenphos, enestrobin, enestroburin, epoxiconazole, ethaboxam,ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol,fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil,fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentin acetate,fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumorph,fluopicolide, fluopyram, fluoroimide, fluoxastrobin, fluquinconazole,flusilazole, flusulfamide, flutianil, flutolanil, flutriafol,fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminium,fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acetates,GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalilsulfate, imibenconazole, iminoctadine, iminoctadine triacetate,iminoctadine tris(albesilate), iodocarb, ipconazole, ipfenpyrazolone,iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam,isotianil, kasugamycin, kasugamycin hydrochloride hydrate,kresoxim-methyl, laminarin, mancopper, mancozeb, mandipropamid, maneb,mefenoxam, mepanipyrim, mepronil, meptyl-dinocap, mercuric chloride,mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam,metam-ammonium, metam-potassium, metam-sodium, metconazole,methasulfocarb, methyl iodide, methyl isothiocyanate, metiram,metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam,nitrothal-isopropyl, nuarimol, octhilinone, ofurace, oleic acid (fattyacids), orysastrobin, oxadixyl, oxine-copper, oxpoconazole fumarate,oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen,pentachlorophenol, pentachlorophenyl laurate, penthiopyrad,phenylmercury acetate, phosphonic acid, phthalide, picoxystrobin,polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassiumhydroxyquinoline sulfate, probenazole, prochloraz, procymidone,propamocarb, propamocarb hydrochloride, propiconazole, propineb,proquinazid, prothioconazole, pyraclostrobin, pyrametostrobin,pyraoxystrobin, pyrazophos, pyribencarb, pyributicarb, pyrifenox,pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen,quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam,simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodiumpentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, tar oils,tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole,thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl,tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole,tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole,validamycin, valifenalate, valiphenal, vinclozolin, zineb, ziram,zoxamide, Candida oleophila, Fusarium oxysporum, Gliocladium spp.,Phlebiopsis gigantea, Streptomyces griseoviridis, Trichoderma spp.,(RS)—N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide,1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate,1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane,2-(2-heptadecyl-2-imidazolin-1-yl)ethanol,2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide,2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride,2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine,4-(2-nitroprop-1-enyl)phenyl thiocyanateme, ampropylfos, anilazine,azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox,bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl,bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmiumcalcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone,chloraniformethan, chlorfenazole, chlorquinox, climbazole, copperbis(3-phenylsalicylate), copper zinc chromate, cufraneb, cuprichydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram,decafentin, dichlone, dichlozoline, diclobutrazol, dimethirimol,dinocton, dinosulfon, dinoterbon, dipyrithione, ditalimfos, dodicin,drazoxolon, EBP, ESBP, etaconazole, etem, ethirim, fenaminosulf,fenapanil, fenitropan, fluotrimazole, furcarbanil, furconazole,furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin,halacrinate, Hercules 3944, hexylthiofos, ICIA0858, isopamphos,isovaledione, mebenil, mecarbinzid, metazoxolon, methfuroxam,methylmercury dicyandiamide, metsulfovax, milneb, mucochloric anhydride,myclozolin, N-3,5-dichlorophenyl-succinimide,N-3-nitrophenylitaconimide, natamycin,N-ethylmercurio-4-toluenesulfonanilide, nickelbis(dimethyldithiocarbamate), OCH, phenylmercurydimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb;prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyroxychlor,pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole,rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor,thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid,triamiphos, triarimol, triazbutil, trichlamide, urbacid, zarilamid, andany combinations thereof.

Additionally, the compounds described herein may be combined with otherpesticides, including insecticides, nematocides, miticides,arthropodicides, bactericides or combinations thereof that arecompatible with the compounds of the present disclosure in the mediumselected for application, and not antagonistic to the activity of thepresent compounds to form pesticidal mixtures and synergistic mixturesthereof. The fungicidal compounds of the present disclosure may beapplied in conjunction with one or more other pesticides to control awider variety of undesirable pests. When used in conjunction with otherpesticides, the presently claimed compounds may be formulated with theother pesticide(s), tank-mixed with the other pesticide(s) or appliedsequentially with the other pesticide(s). Typical insecticides include,but are not limited to: 1,2-dichloropropane, abamectin, acephate,acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile,alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin,allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan,amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine,athidathion, azadirachtin, azamethiphos, azinphos-ethyl,azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin,bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin,bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron,borax, boric acid, bromfenvinfos, bromocyclen, bromo-DDT, bromophos,bromophos-ethyl, bufencarb, buprofezin, butacarb, butathiofos,butocarboxim, butonate, butoxycarboxim, cadusafos, calcium arsenate,calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran,carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan,cartap, cartap hydrochloride, chlorantraniliprole, chlorbicyclen,chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride,chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron,chlormephos, chloroform, chloropicrin, chlorphoxim, chlorprazophos,chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide,cinerin I, cinerin II, cinerins, cismethrin, cloethocarb, closantel,clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate,copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos,crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate,cyantraniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin,cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran,deltamethrin, demephion, demephion-O, demephion-S, demeton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos,diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos,dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor,dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos,dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran,diofenolan, dioxabenzofos, dioxacarb, dioxathion, disulfoton,dithicrofos, d-limonene, DNOC, DNOC-ammonium, DNOC-potassium,DNOC-sodium, doramectin, ecdysterone, emamectin, emamectin benzoate,EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane,eprinomectin, esdepalléthrine, esfenvalerate, etaphos, ethiofencarb,ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate,ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide,etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor,fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb,fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion,fenthion, fenthion-ethyl, fenvalerate, fipronil, flonicamid,flubendiamide, flucofuron, flucycloxuron, flucythrinate, flufenerim,flufenoxuron, flufenprox, fluvalinate, fonofos, formetanate, formetanatehydrochloride, formothion, formparanate, formparanate hydrochloride,fosmethilan, fospirate, fosthietan, furathiocarb, furethrin,gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD,heptachlor, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon,hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imiprothrin,indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos,isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane,isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos,juvenile hormone I, juvenile hormone II, juvenile hormone III, kelevan,kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos,lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben,mazidox, mecarbam, mecarphon, menazon, mephosfolan, mercurous chloride,mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion,methiocarb, methocrotophos, methomyl, methoprene, methoxychlor,methoxyfenozide, methyl bromide, methyl isothiocyanate,methylchloroform, methylene chloride, metofluthrin, metolcarb,metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime,mipafox, mirex, molosultap, monocrotophos, monomehypo, monosultap,morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine,nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron,noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydeprofos,oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl,penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin,phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor,phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos,pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite,potassium thiocyanate, pp′-DDT, prallethrin, precocene I, precocene II,precocene III, primidophos, profenofos, profluralin, promacyl,promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos,prothoate, protrifenbute, pyraclofos, pyrafluprole, pyrazophos,pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyridaben,pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyrimitate,pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl,quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadilla,schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodiumfluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide,spinetoram, spinosad, spiromesifen, spirotetramat, sulcofuron,sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfurylfluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide,tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, TEPP,terallethrin, terbufos, tetrachloroethane, tetrachlorvinphos,tetramethrin, tetramethylfluthrin, theta-cypermethrin, thiacloprid,thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate,thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium,thiosultap-monosodium, thuringiensin, tolfenpyrad, tralomethrin,transfluthrin, transpermethrin, triarathene, triazamate, triazophos,trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumuron,trimethacarb, triprene, vamidothion, vaniliprole, XMC, xylylcarb,zeta-cypermethrin, zolaprofos, and any combinations thereof.

Additionally, the compounds described herein may be combined withherbicides that are compatible with the compounds of the presentdisclosure in the medium selected for application, and not antagonisticto the activity of the present compounds to form pesticidal mixtures andsynergistic mixtures thereof. The fungicidal compounds of the presentdisclosure may be applied in conjunction with one or more herbicides tocontrol a wide variety of undesirable plants. When used in conjunctionwith herbicides, the presently claimed compounds may be formulated withthe herbicide(s), tank-mixed with the herbicide(s) or appliedsequentially with the herbicide(s). Typical herbicides include, but arenot limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB;2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor,acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim,allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone,amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl,amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton,atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC,beflubutamid, benazolin, bencarbazone, benfluralin, benfuresate,bensulfuron, bensulide, bentazone, benzadox, benzfendizone, benzipram,benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron,bicyclopyrone, bifenox, bilanafos, bispyribac, borax, bromacil,bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon,butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron,butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole,calcium chlorate, calcium cyanamide, cambendichlor, carbasulam,carbetamide, carboxazole chlorprocarb, carfentrazone, CDEA, CEPC,chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine,chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop,chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlornitrofen,chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham,chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin,cinosulfuron, cisanilide, clethodim, cliodinate, clodinafop, clofop,clomazone, clomeprop, cloprop, cloproxydim, clopyralid, cloransulam,CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron,cyanatryn, cyanazine, cycloate, cyclosulfamuron, cycloxydim, cycluron,cyhalofop, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon,dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba,dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P,diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron,difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate,dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano,dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb,dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron,DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon,esprocarb, ethalfluralin, ethametsulfuron, ethidimuron, ethiolate,ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid,etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P,fenoxasulfone, fenteracol, fenthiaprop, fentrazamide, fenuron, ferroussulfate, flamprop, flamprop-M, flazasulfuron, florasulam, fluazifop,fluazifop-P, fluazolate, flucarbazone, flucetosulfuron, fluchloralin,flufenacet, flufenican, flufenpyr, flumetsulam, flumezin, flumiclorac,flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen,fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil,flupropanate, flupyrsulfuron, fluridone, flurochloridone, fluroxypyr,flurtamone, fluthiacet, fomesafen, foramsulfuron, fosamine, furyloxyfen,glufosinate, glufosinate-P, glyphosate, halauxifen, halosafen,halosulfuron, haloxydine, haloxyfop, haloxyfop-P, hexachloroacetone,hexaflurate, hexazinone, imazamethabenz, imazamox, imazapic, imazapyr,imazaquin, imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil,iodomethane, iodosulfuron, ioxynil, ipazine, ipfencarbazone, iprymidam,isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin,isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole,isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron,MAA, MAMA, MCPA, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb,mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam,metamifop, metamitron, metazachlor, metazosulfuron, metflurazon,methabenzthiazuron, methalpropalin, methazole, methiobencarb,methiozolin, methiuron, methometon, methoprotryne, methyl bromide,methyl isothiocyanate, methyldymron, metobenzuron, metobromuron,metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate,monalide, monisouron, monochloroacetic acid, monolinuron, monuron,morfamquat, MSMA, naproanilide, napropamide, naptalam, neburon,nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen,norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene,orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon,oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat,pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol,pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham,phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate,picloram, picolinafen, pinoxaden, piperophos, potassium arsenite,potassium azide, potassium cyanate, pretilachlor, primisulfuron,procyazine, prodiamine, profluazol, profluralin, profoxydim,proglinazine, prometon, prometryn, propachlor, propanil, propaquizafop,propazine, propham, propisochlor, propoxycarbazone, propyrisulfuron,propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor,pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazolynate,pyrazosulfuron, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor,pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac,pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine,quinonamid, quizalofop, quizalofop-P, rhodethanil, rimsulfuron,saflufenacil, S-metolachlor, sebuthylazine, secbumeton, sethoxydim,siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodiumazide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone,sulfometuron, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA,tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim,terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn,tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin,thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb,tiocarbazil, tioclorim, topramezone, tralkoxydim, triafamone,tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, triclopyr,tridiphane, trietazine, trifloxysulfuron, trifluralin, triflusulfuron,trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan,tritac, tritosulfuron, vernolate, and xylachlor.

Another embodiment of the present disclosure is a method for the controlor prevention of fungal attack. This method comprises applying to thesoil, plant, roots, foliage, or locus of the fungus, or to a locus inwhich the infestation is to be prevented (for example applying to cerealor grape plants), a fungicidally effective amount of one or more of thecompounds of Formula I. The compounds are suitable for treatment ofvarious plants at fungicidal levels, while exhibiting low phytotoxicity.The compounds may be useful both in a protectant and/or an eradicatefashion.

The compounds have been found to have significant fungicidal effectparticularly for agricultural use. Many of the compounds areparticularly effective for use with agricultural crops and horticulturalplants.

It will be understood by those in the art that the efficacy of thecompound for the foregoing fungi establishes the general utility of thecompounds as fungicides.

The compounds have broad ranges of activity against fungal pathogens.Exemplary pathogens may include, but are not limited to, causing agentof wheat leaf blotch (Mycosphaerella graminicola; impect stage: Septoriatritici), wheat brown rust (Puccinia triticina), wheat stripe rust(Puccinia striiformis), scab of apple (Venturia inaequalis), powderymildew of grapevine (Uncinula necator), barley scald (Rhynchosporiumsecalis), blast of rice (Magnaporthe grisea), rust of soybean(Phakopsora pachyrhizi), glume blotch of wheat (Leptosphaeria nodorum),powdery mildew of wheat (Blumeria graminis f sp. tritici), powderymildew of barley (Blumeria graminis f sp. hordei), powdery mildew ofcucurbits (Erysiphe cichoracearum), anthracnose of cucurbits (Glomerellalagenarium), leaf spot of beet (Cercospora beticola), early blight oftomato (Alternaria solani), and spot blotch of barley (Cochliobolussativus). The exact amount of the active material to be applied isdependent not only on the specific active material being applied, butalso on the particular action desired, the fungal species to becontrolled, and the stage of growth thereof, as well as the part of theplant or other product to be contacted with the compound. Thus, all thecompounds, and formulations containing the same, may not be equallyeffective at similar concentrations or against the same fungal species.

The compounds are effective in use with plants in a disease-inhibitingand phytologically acceptable amount. The term “disease-inhibiting andphytologically acceptable amount” refers to an amount of a compound thatkills or inhibits the plant disease for which control is desired, but isnot significantly toxic to the plant. This amount will generally be fromabout 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm beingpreferred. The exact concentration of compound required varies with thefungal disease to be controlled, the type of formulation employed, themethod of application, the particular plant species, climate conditions,and the like. A suitable application rate is typically in the range fromabout 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per squaremeter, g/m²).

Any range or desired value given herein may be extended or alteredwithout losing the effects sought, as is apparent to the skilled personfor an understanding of the teachings herein.

The compounds of Formula I may be made using well-known chemicalprocedures. Intermediates not specifically mentioned in this disclosureare either commercially available, may be made by routes disclosed inthe chemical literature, or may be readily synthesized from commercialstarting materials utilizing standard procedures.

General Schemes

The following schemes illustrate approaches to generating picolinamidecompounds of Formula (I). The following descriptions and examples areprovided for illustrative purposes and should not be construed aslimiting in terms of substituents or substitution patterns.

Compounds of Formula 1.5, where R₁ is as originally defined, can beprepared according to the methods outlined in Scheme 1, steps a-g.Compounds of Formula 1.1, where R₁ is as originally defined, can beobtained by reaction of the dianion of an ester of Formula 1.0 formed bytreatment with lithium diisopropyl amide (LDA) at −50° C., with an alkylhalide or allyl halide in a solvent such as tetrahydrofuran (THF) atcryogenic temperatures such as −78° C., as shown in a. Compounds ofFormula 1.2, where R₁ is as originally defined, can be obtained bytreating compounds of Formula 1.1, where R₁ is an alkenyl functionality,with hydrogen gas in the presence of a catalyst such as palladium oncarbon (Pd/C) in a solvent such as ethyl acetate (EtOAc), as shown in b.Compounds of Formula 1.3, where R₁ is as originally defined can beprepared from compounds of Formula 1.1, where R₁ is as defined above,and Formula 1.2, where R₁ is as defined above, by treating with analkylating agent such as 4-methoxybenzyl 2,2,2-trichloroacetimidate inthe presence of an acid such as camphor sulfonic acid (CSA) in a solventsuch as dichloromethane (DCM), as depicted in c. Aldehydes of Formula1.4, where R₁ is as originally defined, can be obtained by the reductionof esters of Formula 1.3, where R₁ is as defined above, using a catalystsuch as chlorobis(cyclooctene)iridium(I) dimer in the presence of areducing agent such as diethylsilane (Et₂SiH) in a solvent such as DCM,as shown in d. Aldehydes of Formula 1.4, where R₁ is as originallydefined, can also be obtained by reduction of esters of Formula 1.3,where R₁ is as defined above, using hydride reducing agents, such aslithium aluminum hydride (LiAlH₄, LAH) in ethereal solvents, givingalcohols of Formula 1.6, where R₁ is as defined above, as depicted in e.Oxidation of alcohols of Formula 1.6, where R₁ is as defined above,using oxidation reagents such as sulfur trioxide-pyridine complex(SO₃-pyridine/dimethyl sulfoxide (DMSO)) in solvents such as DCM,furnish the aldehydes of Formula 1.4, where R₁ is as originally defined,as depicted in f. The addition of metallated alkenes such as vinylmagnesium bromide to aldehydes of Formula 1.4, where R₁ is as definedabove, in a solvent such as THF at −78° C. affords allylic alcohols ofFormula 1.5, where R₁ is as originally defined, as depicted in g.

Compounds of Formulas 2.0 and 2.1, where R₁ and R₂ are as originallydefined, but R₂ is not acyl or hydrogen, can be prepared as shown inScheme 2, steps a-b. Alcohols of Formula 1.5, where R₁ is as originallydefined, can be alkylated to give compounds of Formula 2.0, where R₁ andR₂ are as defined above, by deprotonation with a base such as sodiumhydride (NaH) in an aprotic solvent such as N,N-dimethylformamide (DMF),followed by treatment with an alkylating agent, such ascyclopropylmethyl bromide, at an elevated temperature such as 50° C., asshown in a. Alternatively, alcohols of Formula 1.5, where R₁ is asdefined above, can be arylated by treating with an arylating agent suchas triphenylbismuth(V)diacetate in the presence of a copper catalystsuch as diacetoxycopper and a base such asN,N-dicyclohexyl-N-methylamine in a solvent such as toluene at anelevated temperature such as 60° C. to give compounds of Formula 2.1,where R₁ and R₂ are as defined above, as depicted in b.

Compounds of Formula 3.5, where both R₁ and R₂ are as originallydefined, but R₂ is not acyl or hydrogen, and X is Boc, can be preparedas outlined in Scheme 3, steps a-e. Compounds of Formula 3.2, where R₁,R₂ and X are as defined above, can be prepared from compounds of Formula3.0, where R₁ is as originally defined, R₂ is not acyl or alkenyl, and Xis Boc, by treatment with an alkylborane reagent, such as9-borabicyclo[3.3.1]nonane (9-BBN), in a solvent such as THF, at atemperature between ambient room temperature and about 50° C. Then, themixture can be treated with an aqueous basic solution, such as potassiumphosphate (K₃PO₄), a brominated olefin, such as a compound of Formula3.1, where X is Boc (prepared as in Singh et al. Org. Lett. 2003, 17,3155-3158), and a catalyst, such as[1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl₂(dppf))at ambient room temperature to about 55° C. to produce a compound ofFormula 3.2 as shown in step a. Compounds of the Formula 3.3, where R₁,R₂ and X are as defined above, can be prepared from enamides,generalized by Formula 3.2, where R₁, R₂, and X are as defined above,using an asymmetric hydrogenation reaction employing a catalyst such as(+)-1,2-bis((2S,5S)-2,5-diethylphospholano)benzene(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate ((S,S)-Et-DuPHOS-Rh) under ahydrogen atmosphere at a pressure between 40 and 200 pounds per squareinch (psi) in a solvent such as methanol (MeOH) as shown in step b. Asshown in step c, compounds of Formula 3.3 can be converted to compoundsof Formula 3.4, where R₁, R₂ and X are as defined above, by removing thepara-methoxybenzyl (PMB) protecting group using an oxidant such as2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in an aqueous DCMsolvent mixture at a temperature of about 0° C. Compounds of Formula3.5, where R₁, R₂, and X are as defined above, can be prepared fromcompounds of Formula 3.4, where R₁, R₂, and X are as defined above andthe carboxylic acid is protected as either the methyl (Me) or benzyl(Bn) ester, by treating with a hydroxide base, such as lithium hydroxide(LiOH), in an aqueous THF solvent mixture, as shown in step d.Additionally, compounds of Formula 3.5, where R₁ and X are as definedabove and R₂ is as originally defined, but not benzyl, acyl, orhydrogen, can be prepared from compounds of Formula 3.4 wherein thecarboxylic acid is protected as the Bn ester and R₁, R₂, and X are asdefined above by treatment with hydrogen gas in the presence of acatalyst such as Pd/C, in a solvent such as EtOAc, as shown in step e.

Compounds of Formula 4.0, where R₁ and R₂ are as originally defined, butR₂ is not acyl or hydrogen, and X is Boc, can be prepared according tothe methods outlined in Scheme 4. Compounds of Formula 4.0, can beobtained from compounds of Formula 3.5, where R₁ and R₂ are as definedabove and X is Boc, by the addition of a solution of compounds ofFormula 3.5 in a halogenated solvent such as DCM or an aromatic solventsuch as toluene to a mixture of a base, such as 4-dimethylaminopyridine(DMAP), and a mixed anhydride, such as 2-methyl-6-nitrobenzoic anhydride(MNBA), in either a halogenated solvent such as DCM or an aromaticsolvent such as toluene at a temperature between about 21° C. and about60° C. over a period of 4-12 hours (h), as shown in a.

Compounds of Formulas 5.2 and 5.3 can be prepared through the methodsshown in Scheme 5, steps a-d. Alcohols of Formula 5.0 are accessed fromcompounds of Formula 4.0, where R₁ is as originally defined, R₂ isbenzyl, and X is Boc, by treatment with hydrogen gas in the presence ofa catalyst such as Pd/C, in a solvent such as THF, as shown in b.Compounds of Formula 5.1, where R₁ is as originally defined, R₂ is acyl,and X is Boc, can be prepared from compounds of Formula 5.0, where R₁and X are as defined above, by treating with a carbonyl chloride such ascyclopropanecarbonyl chloride in the presence of an amine base such asDMAP, in a mixed solvent system such as pyridine and DCM, as shown instep c. Compounds of Formula 5.2, where R₁ and R₂ are as originallydefined and X and Y are hydrogen, can be obtained from compounds ofFormula 4.0 or 5.1, where R₁ and R₂ are as originally defined, and X isBoc, by treating with an acid, such as a 4.0 Molar (M) hydrogen chloride(HCl) solution in dioxane, in a solvent such as DCM, as shown in a. Theresulting hydrochloride salt may be neutralized prior to use to give thefree amine or neutralized in situ in step d. Compounds of Formula 5.3,where R₁ and R₂ are as originally defined, can be prepared fromcompounds of Formula 5.2 by treatment with 3-hydroxy-4-methoxypicolinicacid in the presence of a base, such as 4-methylmorpholine, and apeptide coupling reagent, such asO-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HATU) orbenzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate(PyBOP), in an aprotic solvent such as DCM, as shown in d.

Compounds of Formula 6.0, where R₁, R₂ and R₄ are as originally defined,can be prepared by the method shown in Scheme 6. Compounds of Formula6.0 can be prepared from compounds of Formula 5.3, where R₁ and R₂ areas originally defined, by treatment with the appropriate alkyl halidewith or without a reagent such as sodium iodide (NaI) and an alkalicarbonate base such as sodium carbonate (Na₂CO₃) or potassium carbonate(K₂CO₃) in a solvent such as acetone or by treatment with an acyl halidein the presence of an amine base, such as pyridine, triethylamine (TEA),DMAP, or mixtures thereof in an aprotic solvent such as DCM, as shown instep a.

EXAMPLES Example 1 Step 1: Preparation of (S)-methyl2-((S)-1-hydroxyethyl)-5-methylhex-4-enoate

To a solution of diisopropylamine (19.93 milliliters (mL), 142millimoles (mmol)) in anhydrous THF (99 mL) at −50° C. (deficient dryice/acetone bath) was added n-butyllithium (n-BuLi; 54.3 mL, 130 mmol,2.5 M in hexanes). This solution was removed from the cold bath for 15minutes (min), then re-cooled to −50° C. To the lithium diisopropylamide(LDA) was added a solution of (S)-methyl 3-hydroxybutanoate (6.64 ml,59.3 mmol) in THF (20.0 mL) dropwise over 15 min using a cannula. Thissolution was allowed to warm to −30° C. over 30 min, stirred at −30° C.for 1 h, and recooled to −78° C. To the enolate was added a solution of1-bromo-3-methylbut-2-ene (13.7 mL, 119 mmol) in anhydrous1,2-dimethoxyethane (20.0 mL, 193 mmol) dropwise over 15 min. The coldbath was at −60° C. after 1 h at which time the reaction flask wasremoved from the bath and stirred without cooling for 1.5 h. Thereaction was quenched by the addition of sat. aq. ammonium chloride(NH₄Cl; 50 mL), diluted with EtOAc (50 mL), and the phases wereseparated. The aqueous phase was further extracted with EtOAc (2×50 mL)and the combined organic extracts were washed with sat. aq. sodiumchloride (NaCl, brine; 50 mL), dried over sodium sulfate Na₂SO₄,filtered, and concentrated to dryness. The crude residue was purified byflash column chromatography (120 grams (g) silica gel (SiO₂), 0→40%EtOAc/hexanes) to afford the title compound (9.5 g, 51.0 mmol, 86%) as aslightly yellow oil: IR (thin film) 3452, 2971, 2929, 1730, 1437, 1198,1160 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 5.11-5.01 (m, 1H), 3.92 (p, J=6.3Hz, 1H), 3.70 (s, 3H), 2.78 (s, 1H), 2.46-2.28 (m, 3H), 1.69 (d, J=1.4Hz, 3H), 1.62 (s, 3H), 1.23 (d, J=6.4 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃)δ 175.54, 134.14, 120.30, 67.78, 52.72, 51.52, 27.90, 25.73, 21.46,17.64.

Example 1 Step 2: Preparation of (S)-methyl2-((S)-1-hydroxyethyl)-5-methylhexanoate

To a well stirred solution of (S)-methyl2-((S)-1-hydroxyethyl)-5-methylhex-4-enoate (9.5 g, 51.0 mmol) in MeOH(51 mL) was added 10% Pd/C (0.543 g, 5.10 mmol). The reaction was putunder a hydrogen atmosphere (balloon) and stirred at room temperaturefor 20 h. The mixture was filtered through a plug of Celite® and theplug was washed with MeOH (20 mL). The filtrate and washes werecombined, the solvent was removed under reduced pressure, and theresidue was dissolved in DCM (50 mL). The solution was passed through aphase separator to remove residual water (H₂O), and the solvent wasremoved under reduced pressure to afford the title compound (9.45 g,50.2 mmol, 98%) as a slightly yellow oil: IR (thin film) 3451, 2954,2871, 1736, 1719, 1169 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 3.91 (p, J=6.4Hz, 1H), 3.72 (s, 3H), 2.77 (s, 1H), 2.36 (ddd, J=9.2, 6.3, 5.0 Hz, 1H),1.72-1.45 (m, 3H), 1.28-1.05 (m, 5H), 0.88 (dd, J=6.6, 3.2 Hz, 6H); ¹³CNMR (75 MHz, CDCl₃) δ 176.13, 68.55, 53.29, 51.67, 36.55, 28.16, 27.37,22.74, 22.44, 21.68.

Example 1 Step 3: Preparation of (S)-methyl2-((S)-1-((4-methoxybenzyl)oxy)ethyl)-5-methylhexanoate

To a solution of (S)-methyl 2-((S)-1-hydroxyethyl)-5-methylhexanoate(5.00 g, 26.6 mmol) and((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonicacid (camphorsulfonic acid, CSA; 0.617 g, 2.66 mmol) in DCM (53.1 mL)was added 4-methoxybenzyl 2,2,2-trichloroacetimidate (8.27 mL, 39.8mmol) at 0° C. The reaction mixture was removed from the cold bath andstirred at room temperature for 17 h. Hexane (50 mL) was added to thereaction and the precipitate was removed by filtration. The solids werewashed with hexanes (2×10 mL), Celite® (2 scoopula tip-fulls) was addedto the combined filtrate and washes, and the solvent was removed underreduced pressure. The resulting adsorbed material was directly loadedonto a column and purified using flash column chromatography (80 g SiO₂,0→35% EtOAc/hexanes) to afford the title compound (6.3 g, 20.4 mmol,77%) as a colorless oil; ¹H NMR (400 MHz, CDCl₃) δ 7.24-7.16 (m, 2H),6.89-6.79 (m, 2H), 4.49 (d, J=11.2 Hz, 1H), 4.33 (d, J=11.1 Hz, 1H),3.75 (s, 3H), 3.74-3.62 (m, 4H), 2.49 (ddd, J=10.7, 8.2, 4.0 Hz, 1H),1.62-1.40 (m, 3H), 1.23-1.16 (m, 3H), 1.16-1.03 (m, 2H), 0.87 (d, J=3.9Hz, 3H), 0.85 (d, J=3.9 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 175.03,159.10, 130.63, 129.14, 113.62, 76.16, 70.71, 55.11, 52.64, 51.25,36.58, 27.97, 26.00, 22.69, 22.17, 17.08; ESIMS m/z 331 ([M+Na]⁺).

Example 1 Steps 4 and 5: Preparation of(3S,4R)-4-((S)-1-((4-methoxy-benzyl)oxy)ethyl)-7-methyloct-1-en-3-ol and(3R,4R)-4-((S)-1-((4-methoxybenzyl)oxy)ethyl)-7-methyloct-1-en-3-ol

Step 4

To a solution of (S)-methyl2-((S)-1-((4-methoxybenzyl)oxy)ethyl)-5-methylhexanoate (6.00 g, 19.5mmol) and chlorobis(cyclooctene)-iridium(I) dimer (0.349 g, 0.389 mmol)in dry DCM (19.5 mL) was slowly added Et₂SiH (3.76 mL, 29.2 mmol) at 0°C. The flask was removed from the cold bath and the reaction was stirredat room temperature for 20 h under nitrogen (N₂). The reaction mixturewas transferred via cannula to an ice-cooled mixture of diethyl ether(Et₂O; 60 mL) and 2 Normal (N) HCl (20 mL) over 15 min. The mixture wasremoved from the cold bath and stirred at room temperature for 30 min.The phases were separated and the aq. phase was further extracted withEt₂O (2×50 mL). The organics were combined, washed with sat. aq. sodiumbicarbonate (NaHCO₃; 25 mL) and brine (25 mL), dried over Na₂SO₄,filtered, and the filtrate treated with Celite® (5 scoopula tip-fulls).The solvent was removed under reduced pressure and the resultingadsorbed material was directly loaded onto a column and purified usingflash column chromatography (120 g SiO₂, 0→75% EtOAc/hexanes) to affordthe intermediate aldehyde,(S)-2-((S)-1-((4-methoxybenzyl)oxy)ethyl)-5-methylhexanal.

Step 5

The intermediate aldehyde was dissolved in THF (30 mL), the mixture wascooled to −78° C., vinylmagnesium bromide (29.2 mL, 29.2 mmol, 1M inTHF) was slowly added, and the resulting solution was stirred for 30min. The reaction was removed from the cold bath, stirred at roomtemperature for 30 min, and quenched by the addition of sat. aq. NH₄Cl(30 mL). The phases were separated, and the aq. phase was furtherextracted with Et₂O (3×50 mL). The combined organics were dried overNa₂SO₄, filtered, and concentrated to dryness. The residue was dissolvedin DCM (20 mL) and the resulting solution was treated with Celite® (5scoopula tip-fulls). The solvent was removed under reduced pressure andthe resulting adsorbed material was directly loaded onto a column andpurified using flash column chromatography (220 g SiO₂, 0→15%acetone/hexanes) to afford the individual diastereomers as colorlessoils:

(3S,4R)-4-((S)-1-((4-methoxybenzyl)oxy)ethyl)-7-methyloct-1-en-3-ol(2.35 g, 7.67 mmol, 39%): ¹H NMR (400 MHz, CDCl₃) δ 7.27-7.19 (m, 2H),6.91-6.82 (m, 2H), 5.84 (ddd, J=17.2, 10.6, 4.7 Hz, 1H), 5.29 (app dt,J=17.2, 1.9 Hz, 1H), 5.16 (app dt, J=10.6, 1.9 Hz, 1H), 4.58 (d, J=11.0Hz, 1H), 4.53-4.45 (m, 1H), 4.27 (d, J=10.9 Hz, 1H), 3.83 (d, J=4.3 Hz,1H), 3.79 (s, 3H), 3.76-3.65 (m, 1H), 1.52-1.26 (m, 7H), 1.20-1.06 (m,2H), 0.85 (app dd, J=6.6, 2.2 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ159.33, 139.16, 130.02, 129.54, 114.61, 113.88, 76.55, 72.08, 70.65,55.26, 49.31, 37.35, 28.25, 23.51, 22.63, 22.52, 17.71; ESIMS m/z 329([M+Na]⁺).

(3R,4R)-4-((S)-1-((4-methoxybenzyl)oxy)ethyl)-7-methyloct-1-en-3-ol(1.48 g, 4.83 mmol, 25%): ¹H NMR (400 MHz, CDCl₃) δ 7.30-7.22 (m, 2H),6.91-6.83 (m, 2H), 5.89 (ddd, J=17.1, 10.3, 6.7 Hz, 1H), 5.24 (ddd,J=17.2, 1.8, 1.2 Hz, 1H), 5.12 (ddd, J=10.4, 1.8, 1.1 Hz, 1H), 4.58 (d,J=11.1 Hz, 1H), 4.35 (d, J=11.1 Hz, 1H), 4.22-4.13 (m, 1H), 3.80 (s,3H), 3.70 (p, J=6.3 Hz, 1H), 3.66 (d, J=3.2 Hz, 1H), 1.56 (tt, J=6.8,5.2 Hz, 1H), 1.49-1.24 (m, 6H), 1.19-1.08 (m, 2H), 0.84 (dd, J=6.7, 2.0Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ 159.24, 140.20, 130.22, 129.41,115.17, 113.87, 78.10, 75.83, 70.43, 55.28, 48.98, 36.07, 28.53, 26.08,22.52, 17.93; ESIMS m/z 329 ([M+Na]⁺).

Example 1 Step 6: Preparation of(2R,3S)-2-benzyl-3-(4-methoxybenzyl)-oxy)butan-1-ol

To a stirred suspension of LAH (2.77 g, 73.1 mmol) in anhydrous Et₂O(140 mL) was added (2S,3S)-methyl2-benzyl-3-((4-methoxybenzyl)oxy)butanoate (8.0 g, 24.36 mmol) dissolvedin Et₂O (104 mL) dropwise at 0° C. The reaction was stirred at 0° C. for15 min, followed by warming to room temperature and stirring for 1 h.The reaction was recooled to 0° C. and carefully quenched by thesimultaneous dropwise addition of H₂O (2.8 mL) and 1N sodium hydroxide(NaOH; 2.8 mL). The mixture was filtered and the aluminum salts werewashed with Et₂O (50 mL). The filtrate was treated with Celite® (20 g)and concentrated to give a solid. The adsorbed material was purifiedusing flash column chromatography (120 g SiO₂ column, 0→60%EtOAc/hexane) to afford the title compound (5.38 g, 74%) as a clear oil:¹H NMR (400 MHz, CDCl₃) δ 7.30-7.10 (m, 7H), 6.93-6.84 (m, 2H), 4.59 (d,J=11.2 Hz, 1H), 4.30 (d, J=11.2 Hz, 1H), 3.89 (app dt, J=11.4, 2.9 Hz,1H), 3.80 (s, 3H), 3.66 (app qd, J=6.2, 4.3 Hz, 1H), 3.50 (ddd, J=11.5,6.9, 4.7 Hz, 1H), 2.93-2.85 (m, 1H), 2.75 (app qd, J=13.7, 7.5 Hz, 2H),1.76 (dddt, J=10.9, 6.6, 4.3, 2.3 Hz, 1H), 1.29 (d, J=6.3 Hz, 3H); ¹³CNMR (101 MHz, CDCl₃) δ 159.32, 140.61, 130.35, 129.39, 129.20, 128.36,125.97, 113.93, 70.70, 62.36, 55.31, 47.81, 35.11, 17.67; ESIMS m/z 323([M+Na]⁺).

Example 1 Step 7: (2S,3S)-2-benzyl-3((4-methoxybenzyl)oxy)butanal

To a solution of (2R,3S)-2-benzyl-3((4-methoxybenzyl)oxy)butan-1-ol(5.38 g, 17.91 mmol) in CH₂Cl₂ (90 mL) in a nitrogen flushed 250 mLround bottomed flask was added DMSO (17.9 mL, 25.24 mmol) and TEA (12.5mL, 90 mmol) via syringe followed by sulfur trioxode-pyridine complex(8.55 g, 53.7 mmol) in three equal portions at 0° C. under N₂. Thereaction was removed from the cold bath and allowed to warm to roomtemperature, and stirred for 2 h. The reaction was diluted with ice cold0.5 N HCl (100 mL) and EtOAc (150 mL). The phases were separated and theorganic phase was washed with sat. aq. NaHCO₃ (50 mL) and brine (50 mL).The solution was dried over magnesium sulfate (MgSO₄), filtered, andconcentrated to afford the title compound (5.3 g, 96%) as a yellow oil:¹H NMR (400 MHz, CDCl₃) δ 9.78 (d, J=2.8 Hz, 1H), 7.29-7.09 (m, 7H),6.89 (d, J=8.7 Hz, 2H), 4.56 (d, J=11.3 Hz, 1H), 4.34 (d, J=11.3 Hz,1H), 3.82 (s, 3H), 3.03 (dd, J=14.0, 8.2 Hz, 1H), 2.87 (dd, J=14.0, 6.4Hz, 2H), 2.78-2.55 (m, 1H), 1.29 (d, J=6.4 Hz, 3H); ESIMS m/z 321.3([M+Na]⁺).

Example 1 Step 8: Preparation of(3S,4R,5S)-4-benzyl-5-(4-methoxybenzyl)oxy)-hex-1-en-3-ol

To a 200 mL round-bottomed flask equipped with a magnetic stir bar wereadded (2S,3S)-2-benzyl-3-((4-methoxybenzyl)oxy)butanal (5.34 g, 17.90mmol) and THF (36 mL). The flask was cooled to −78° C. andvinylmagnesium bromide (1.0 M in THF, 36 mL, 36 mmol) was added via asyringe. The reaction was maintained at −78° C. for 1.5 h, quenched withsat. aq. NH₄Cl (25 mL) at −78° C., and then removed from the cold bath.After warming to room temperature, the biphasic mixture was diluted withEtOAc (100 mL), and the phases were separated. The organic phase waswashed with brine (30 mL), dried over MgSO₄, filtered, and concentrated.The oil was purified by flash column chromatography (120 g SiO₂ column,0→100% EtOAc/hexanes) to afford the pure desired isomer (1.18 g), and amixture of the isomers (2.53 g). The mixture was re-purified by flashcolumn chromatography (80 g SiO₂ column, 0→15% acetone/hexanes) toafford clean separation of the isomers in a 2.23:1 ratio ofdiastereomers.

(3S,4R,5S)-4-Benzyl-5-((4-methoxybenzyl)oxy)hex-1-en-3-ol (2.88 g, 49%):¹H NMR (400 MHz, CDCl₃) δ 7.28-7.17 (m, 5H), 7.05-6.98 (m, 2H),6.92-6.84 (m, 2H), 5.91 (ddd, J=17.1, 10.6, 4.4 Hz, 1H), 5.36 (dt,J=17.2, 1.9 Hz, 1H), 5.23 (dt, J=10.6, 1.8 Hz, 1H), 4.65-4.59 (m, 1H),4.56 (d, J=10.9 Hz, 1H), 4.21 (d, J=11.0 Hz, 1H), 3.89 (d, J=2.7 Hz,1H), 3.78 (s, 3H), 3.65 (qd, J=6.3, 3.7 Hz, 1H), 2.72 (d, J=7.3 Hz, 2H),1.78-1.70 (m, 1H), 1.25 (d, J=6.2 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ159.46, 141.10, 139.22, 130.09, 129.57, 129.23, 128.39, 125.91, 115.02,114.01, 75.38, 70.99, 70.74, 55.33, 50.95, 31.46, 17.72; ESIMS m/z 349([M+Na]⁺).

(3R,4R,5S)-4-Benzyl-5-((4-methoxybenzyl)oxy)hex-1-en-3-ol (1.3 g, 22%):¹H NMR (300 MHz, CDCl₃) δ 7.33-7.04 (m, 7H), 6.96-6.78 (m, 2H), 5.96(ddd, J=17.2, 10.4, 5.5 Hz, 1H), 5.25 (dt, J=17.2, 1.7 Hz, 1H), 5.11(dt, J=10.5, 1.6 Hz, 1H), 4.56 (d, J=11.4 Hz, 1H), 4.31 (d, J=11.4 Hz,1H), 4.28-4.22 (m, 1H), 3.82 (s, 3H), 3.72-3.65 (m, 1H), 2.86-2.87 (m,3H), 2.06-1.96 (m, 1H), 1.27 (d, J=6.4 Hz, 3H): ESIMS m/z 349.3([M+Na]⁺).

Example 2 Step 1: Preparation of1-methoxy-4-(((2S,3S)-6-methyl-3-((S)-1-phenoxyallyl)heptan-2-yl)oxy)methyl)benzene

A toluene (12.0 mL) solution of(3S,4R)-4-((S)-1-((4-methoxybenzyl)oxy)ethyl)-7-methyloct-1-en-3-ol(1.10 g, 3.59 mmol), N-cyclohexyl-N-methylcyclohexanamine (1.14 mL, 5.38mmol), triphenylbismuth diacetate (3.01 g, 5.38 mmol), and copper(II)acetate (0.130 g, 0.718 mmol) was heated to 50° C. and stirred at thistemperature for 16 h. Additional triphenylbismuth diacetate (1.00 g) wasadded to push the reaction to completion, and after a total reactiontime of 38 h, the reaction mixture was cooled to room temperature,loaded onto a Celite® plug and purified by flash column chromatography(40 g SiO₂, 0→15% EtOAc/hexanes) to afford the title compound (1.10 g,2.30 mmol, 64%): ¹H NMR (400 MHz, CDCl₃) δ 7.29-7.20 (m, 3H), 6.99-6.86(m, 4H), 6.76-6.68 (m, 2H), 5.85 (ddd, J=17.4, 10.8, 4.8 Hz, 1H),5.27-5.16 (m, 2H), 5.09 (ddt, J=4.8, 3.2, 1.7 Hz, 1H), 4.39 (d, J=10.6Hz, 1H), 4.09 (d, J=10.6 Hz, 1H), 3.76 (s, 3H), 3.64 (dq, J=8.0, 6.2 Hz,1H), 1.68-1.56 (m, 2H), 1.55-1.42 (m, 1H), 1.41-1.17 (m, 6H), 0.88 (appdd, J=6.6, 1.4 Hz, 6H); ESIMS m/z 405 ([M+Na]⁺).

Example 2 Step 2: Preparation of1-methoxy-4-(((2S,3S)-6-methyl-3-((S)-1-propoxyallyl)heptan-2-yl)oxy)methyl)benzene

To a solution of(3S,4R)-4-((S)-1-((4-methoxybenzyl)oxy)ethyl)-7-methyloct-1-en-3-ol(1.40 g, 4.57 mmol) and potassium 2-methylpropan-2-olate (0.564 g, 5.03mmol) in THF (30.5 mL) was added propyl 4-methylbenzenesulfonate (2.15mL, 11.4 mmol). The reaction was stirred at room temperature for 72 h,diluted with H₂O (15 mL), and the phases were separated. The aq. phasewas further extracted with Et₂O (3×25 mL), and the combined organicswere washed with brine (15 mL), dried over Na₂SO₄, filtered, and thefiltrate was treated with Celite® (4 scoopula tip-fulls). The solventwas removed under reduced pressure and the resulting adsorbed materialwas directly loaded onto a column and purified using flash columnchromatography (80 g SiO₂, 0→15% EtOAc/hexanes) to afford the titlecompound (1.30 g, 3.36 mmol, 74%) as a colorless oil: ¹H NMR (400 MHz,CDCl₃) δ 7.30-7.22 (m, 2H), 6.91-6.83 (m, 2H), 5.77-5.63 (m, 1H),5.20-5.14 (m, 1H), 5.13 (d, J=1.1 Hz, 1H), 4.50-4.35 (m, 2H), 3.85-3.77(m, 4H), 3.61 (p, J=6.3 Hz, 1H), 3.43 (app tt, J=9.8, 6.6 Hz, 1H), 3.12(app dt, J=9.1, 6.6 Hz, 1H), 1.69-1.20 (m, 8H), 1.15 (d, J=6.3 Hz, 3H),0.91 (t, J=7.4 Hz, 3H), 0.87 (app dd, J=6.6, 1.1 Hz, 6H); ¹³C NMR (101MHz, CDCl₃) δ 158.98, 138.54, 131.33, 129.16, 116.04, 113.69, 81.66,75.17, 70.57, 70.12, 55.26, 47.97, 38.70, 28.65, 23.69, 23.24, 22.63,16.76, 10.90; ESIMS m/z 371 ([M+Na]⁺).

Example 2 Step 3: Preparation of1-((((2S,3S)-3-((S)-1-(benzyloxy)allyl)-6-methylheptan-2-yl)oxy)methyl)-4-methoxybenzene

To a solution of(3S,4R)-4-((S)-1-((4-methoxybenzyl)oxy)ethyl)-7-methyloct-1-en-3-ol(2.34 g, 7.64 mmol) in DMF (15.3 mL) was added NaH (0.611 g, 15.3 mmol,60% dispersion in mineral oil) at 0° C. After 20 min, benzyl bromide(2.27 mL, 19.1 mmol) was added and the reaction was stirred at 0° C. for20 min, warmed to 45° C., and stirred at this temperature for 16 h. Thereaction was cooled to room temperature and quenched with sat. aq. NH₄Cl(40 mL). The mixture was extracted with Et₂O (3×50 mL), and the combinedorganics were washed with brine (40 mL), dried over Na₂SO₄, filtered,and concentrated to dryness. The residue was purified using flash columnchromatography (120 g SiO₂, 0→20% EtOAc/hexanes) to afford the titlecompound (2.75 g, 6.93 mmol, 91%) as a colorless oil: ¹H NMR (400 MHz,CDCl₃) δ 7.38-7.34 (m, 2H), 7.32-7.25 (m, 3H), 7.22-7.17 (m, 2H),6.87-6.78 (m, 2H), 5.78 (ddd, J=17.4, 9.9, 7.3 Hz, 1H), 5.27-5.18 (m,2H), 4.58 (d, J=12.4 Hz, 1H), 4.42 (d, J=11.2 Hz, 1H), 4.29 (d, J=11.2Hz, 1H), 4.26 (d, J=11.9 Hz, 1H), 4.04-3.96 (m, 1H), 3.77 (s, 3H), 3.64(p, J=6.3 Hz, 1H), 1.73-1.63 (m, 1H), 1.55-1.42 (m, 2H), 1.43-1.21 (m,3H), 1.15 (d, J=6.3 Hz, 3H), 0.86 (d, J=6.6 Hz, 6H); ¹³C NMR (101 MHz,CDCl₃) δ 158.92, 139.07, 137.94, 131.19, 129.17, 128.19, 127.77, 127.47,116.82, 113.65, 81.13, 75.03, 70.36, 70.07, 55.22, 48.17, 38.66, 28.62,23.67, 22.61, 16.84; ESIMS m/z 419 ([M+Na]⁺).

Example 3 Step 1: Preparation of (6S,7S,Z)-benzyl2-((tert-butoxycarbonyl)amino)-7-((S)-1-((4-methoxybenzyl)oxy)ethyl)-10-methyl-6-propoxyundec-2-enoate

To a solution of1-methoxy-4-((((2S,3S)-6-methyl-3-((S)-1-propoxyallyl)heptan-2-yl)oxy)methyl)benzene(1.25 g, 3.59 mmol) in THF (3 mL) was added 9-BBN (10.8 mL, 5.38 mmol,0.5 M in THF) dropwise, and the reaction was stirred at room temperaturefor 6 h. The reaction mixture was carefully treated with an aq. solutionof K₃PO₄ (3 M, 2.152 mL, 6.46 mmol; gas evolution), followed by asolution of (Z)-benzyl 3-bromo-2-((tert-butoxycarbonyl)amino)acrylate(1.30 g, 3.66 mmol) in DMF (3.59 mL), and PdCl₂-dppf (0.262 g, 0.359mmol). The reaction vessel was fitted with an air condenser and slowlywarmed to 55° C. The solution became homogeneous and bright orange after30 min. The reaction was maintained at this temperature for 20 h, atwhich point the color had turned a very dark red (almost black). Thereaction was cooled to room temperature, diluted with H₂O (30 mL), andthe phases were separated. The aq. phase was extracted with Et₂O (3×50mL), and the combined organics were washed with brine (15 mL), driedover Na₂SO₄, filtered, and the filtrate was treated with Celite® (2scoopula tip-fulls). The solvent was removed under reduced pressure andthe resulting adsorbed material was directly loaded onto a column andpurified using flash column chromatography (80 g SiO₂, 0→25%acetone/hexanes) to afford the title compound (1.50 g, 2.397 mmol, 67%)as a colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 7.40-7.29 (m, 5H),7.25-7.20 (m, 2H), 6.88-6.80 (m, 2H), 6.59 (app t, J=7.5 Hz, 1H), 6.15(s, 1H), 5.20 (app d, J=2.2 Hz, 2H), 4.48 (d, J=11.4 Hz, 1H), 4.34 (d,J=11.4 Hz, 1H), 3.78 (s, 3H), 3.57 (p, J=6.2 Hz, 1H), 3.36 (ddd, J=7.3,5.3, 3.7 Hz, 1H), 3.33-3.19 (m, 2H), 2.36-2.16 (m, 2H), 1.72-1.38 (m,16H), 1.38-1.13 (m, 6H), 0.91-0.82 (m, 9H); ¹³C NMR (101 MHz, CDCl₃) δ164.82, 158.99, 153.42, 137.06, 135.73, 131.13, 129.21, 128.52, 128.24,128.22, 113.70, 80.33, 79.43, 74.78, 71.76, 69.86, 67.00, 55.25, 46.35,38.73, 30.64, 28.68, 28.19, 25.39, 23.88, 23.47, 22.64, 22.61, 17.08,10.79; ESIMS m/z 648 ([M+Na]⁺).

Example 3 Step 2: Preparation of (2S,6S,7S)-benzyl2-((tert-butoxycarbonyl)-amino)-7-((S)-1-((4-methoxybenzyl)oxy)ethyl)-10-methyl-6-propoxyundecanoate

A solution of (6S,7S,Z)-benzyl2-((tert-butoxycarbonyl)amino)-7-((S)-1-((4-methoxybenzyl)oxy)ethyl)-10-methyl-6-propoxyundec-2-enoate(1.50 g, 2.40 mmol) in MeOH (9.59 mL) was added to a 45 mL pressurereactor. The system was purged with N₂ for 5 min and then(+)-1,2-bis((2S,5S)-2,5-diethylphospholano)benzene(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate (0.0170 g, 0.0240 mmol) was added. Thesystem was purged with hydrogen gas (200 psi) 3 times, charged to 200psi with hydrogen gas, and stirred at room temperature for 24 h. Thehydrogen was evacuated and the solution was transferred to a roundbottom flask rinsing with EtOAc (10 mL), and the solvent was removedunder reduced pressure. The residue was dissolved in DCM (10 mL) and theresulting solution was treated with Celite® (3 scoopula tip-fulls). Thesolvent was removed under reduced pressure and the resulting adsorbedmaterial was directly loaded onto a column and purified using flashcolumn chromatography (40 g SiO₂, 0→40% EtOAc/hexanes) to afford thetitle compound (1.10 g, 1.752 mmol, 73%) as a colorless oil: ¹H NMR (400MHz, CDCl₃) δ 7.38-7.27 (m, 5H), 7.29-7.21 (m, 2H), 6.90-6.83 (m, 2H),5.21-5.09 (m, 2H), 5.04 (d, J=8.4 Hz, 1H), 4.47 (d, J=11.3 Hz, 1H),4.41-4.27 (m, 2H), 3.78 (s, 3H), 3.63-3.52 (m, 1H), 3.38-3.26 (m, 3H),1.87-1.74 (m, 1H), 1.70-1.17 (m, 22H), 1.16 (d, J=6.2 Hz, 3H), 0.92-0.83(m, 9H); ¹³C NMR (101 MHz, CDCl₃) δ 172.75, 158.98, 155.35, 135.47,131.30, 129.09, 128.57, 128.35, 128.20, 113.70, 79.78, 75.02, 71.89,69.98, 66.92, 55.24, 53.59, 46.51, 38.66, 32.83, 31.98, 28.69, 28.33,23.83, 23.54, 22.66, 22.64, 22.22, 17.13, 10.84; ESIMS m/z 650([M+Na]⁺).

Example 3 Step 3: Preparation of (2S,6S,7S)-benzyl2-((tert-butoxycarbonyl)amino)-7-((S)-1-hydroxyethyl)-10-methyl-6-propoxyundecanoate

To a solution of (2S,6S,7S)-benzyl2-((tert-butoxycarbonyl)amino)-7-((S)-1-((4-methoxybenzyl)oxy)-ethyl)-10-methyl-6-propoxyundecanoate(1.10 g, 1.75 mmol) in H₂O (0.531 mL) and DCM (5.31 mL) was added DDQ(0.418 g, 1.84 mmol) at 0° C. The mixture was stirred vigorously at thistemperature for 1 h and then 1N NaOH (1.84 mL, 1.84 mmol) and H₂O (20mL) were added. The phases were separated and the aqueous phase wasextracted with DCM (3×15 mL). The combined organic extracts were washedwith brine (8 mL), dried over Na₂SO₄, filtered, and the filtrate wastreated with Celite® (2 scoopula tip-fulls). The solvent was removedunder reduced pressure and the resulting adsorbed material was directlyloaded onto a column and purified using flash column chromatography (40g SiO₂, 0→60% EtOAc/hexanes) to afford the title compound (815 mg, 1.61mmol, 92%) as a colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 7.41-7.30 (m,5H), 5.17 (app q, J=12.4 Hz, 2H), 5.07 (d, J=8.5 Hz, 1H), 4.44-4.39 (m,1H), 4.39-4.30 (m, 1H), 3.87-3.75 (m, 1H), 3.54 (app dt, J=9.0, 6.6 Hz,1H), 3.42-3.33 (m, 1H), 3.26 (app dt, J=8.9, 6.6 Hz, 1H), 1.87-1.76 (m,1H), 1.72-1.37 (m, 17H), 1.35-1.07 (m, 7H), 1.04-0.93 (m, 1H), 0.93-0.84(m, 9H); ¹³C NMR (101 MHz, CDCl₃) δ 172.66, 155.32, 135.39, 128.59,128.42, 128.24, 82.50, 79.89, 71.42, 69.10, 66.99, 53.52, 45.46, 37.47,32.82, 28.82, 28.31, 28.28, 25.27, 23.20, 22.68, 22.54, 22.44, 22.06,10.66; ESIMS m/z 530 ([M+Na]⁺).

Example 3 Step 4: Preparation of(2S,6S,7S)-6-(benzyloxy)-2-((tert-butoxycarbonyl)amino)-7-((S)-1-hydroxyethyl)-10-methylundecanoicacid

To a solution of (2S,6S,7S)-methyl6-(benzyloxy)-2-((tert-butoxycarbonyl)amino)-7-((S)-1-hydroxyethyl)-10-methylundecanoate(700 mg, 1.46 mmol) in THF (9.73 mL) and H₂O (4.87 mL) was addedLiOH.H₂O (184 mg, 4.38 mmol), and the reaction was stirred at roomtemperature for 4 h. The reaction was diluted with EtOAc (15 mL) and 0.2M HCl (15 mL), the phases were separated, and the aq. phase was furtherextracted with EtOAc (3×15 mL). The combined organic extracts werewashed with brine (8 mL), dried over Na₂SO₄, filtered, and concentratedto dryness to afford the title compound (600 mg, 1.289 mmol, 88%) as awhite solid: ¹H NMR (400 MHz, CDCl₃) δ 7.31-7.21 (m, 5H), 5.63 (s, 1H),4.57-4.45 (m, 2H), 3.89-3.74 (m, 2H), 3.59-3.52 (m, 1H), 1.92-1.63 (m,2H), 1.63-0.94 (m, 22H), 0.83 (app dd, J=6.6, 2.1 Hz, 6H) (carboxylicacid and alcohol peaks are very broad (not listed)); ¹³C NMR (101 MHz,CDCl₃) δ 179.67, 156.76, 138.11, 128.33, 128.05, 127.64, 80.99, 79.27,71.52, 68.79, 56.30, 46.67, 37.81, 32.72, 29.56, 28.48, 28.27, 25.15,23.19, 22.63, 22.50, 22.21; ESIMS m/z 464 ([M−H]⁻).

Example 3 Step 5: Preparation of(2S,6S,7S)-2-((tert-butoxycarbonyl)amino)-7-((S)-1-hydroxyethyl)-10-methyl-6-propoxyundecanoicacid

A solution of (2S,6S,7S)-benzyl2-((tert-butoxycarbonyl)amino)-7-((S)-1-hydroxyethyl)-10-methyl-6-propoxyundecanoate(815 mg, 1.61 mmol) and 10% Pd/C (85 mg, 0.803 mmol) in THF (5.35 mL)was stirred under a hydrogen atmosphere (balloon pressure) at roomtemperature for 4 h. The hydrogen was removed using a stream of N₂ andthe reaction was filtered through a plug of Celite®. The plug was washedwith DCM (2×5 mL) and the combined filtrate and washes were concentratedto dryness under reduced pressure to afford the title compound (660 mg,1.58 mmol, 98%) as a colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 5.14 (d,J=8.2 Hz, 1H), 4.36-4.26 (m, 1H), 3.95-3.83 (m, 1H), 3.63-3.52 (m, 1H),3.49-3.41 (m, 1H), 3.37-3.27 (m, 1H), 1.93-1.81 (m, 2H), 1.79-0.80 (m,33H) (carboxylic acid peak is very broad (not listed) and alcohol protonis not visible); ¹³C NMR (101 MHz, CDCl₃) δ 175.98, 155.52, 82.43,79.93, 71.50, 69.42, 53.26, 45.32, 37.36, 32.61, 28.69, 28.31, 28.26,25.17, 23.16, 22.66, 22.39, 21.82, 10.63; ESIMS m/z 416 ([M−H]⁻).

Example 4 Preparation of tert-butyl((3S,7S,8S,9S)-8-isopentyl-9-methyl-2-oxo-7-propoxyoxonan-3-yl)carbamate(18)

A solution of(2S,6S,7S)-2-((tert-butoxycarbonyl)amino)-7-((S)-1-hydroxyethyl)-10-methyl-6-propoxyundecanoicacid (627 mg, 1.50 mmol) in anhydrous DCM (80 mL) was added over 12 husing a syringe pump to a stirred solution of MNBA (1.03 g, 3.00 mmol)and DMAP (1.10 g, 9.01 mmol) in DCM (150 mL) at room temperature.Stirring was continued for an additional 7 h then the reaction mixturewas treated with Celite® (5 scoopula tip-fulls). The solvent was removedunder reduced pressure and the resulting adsorbed material was directlyloaded onto a column and purified using flash column chromatography (80g SiO₂, 0→30% EtOAc/hexanes) to afford the title compound (355 mg, 0.888mmol, 59%) as a colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 5.06 (d, J=8.2Hz, 1H), 4.70 (dq, J=10.1, 6.4 Hz, 1H), 4.24-4.14 (m, 1H), 3.50 (app dt,J=9.0, 6.4 Hz, 1H), 3.28-3.19 (m, 1H), 3.13 (app dt, J=8.8, 6.6 Hz, 1H),2.30-2.18 (m, 1H), 2.11 (dddd, J=15.6, 10.1, 7.9, 5.2 Hz, 1H), 1.87 (appdq, J=13.1, 4.6 Hz, 1H), 1.78-1.35 (m, 16H), 1.31 (d, J=6.3 Hz, 3H),1.24-1.03 (m, 3H), 0.96-0.75 (m, 10H); ¹³C NMR (101 MHz, CDCl₃) δ173.11, 154.94, 79.93, 79.70, 73.53, 70.41, 52.46, 46.66, 34.41, 33.63,29.03, 28.75, 28.33, 26.26, 23.30, 22.61, 22.44, 19.26, 17.80, 10.88;ESIMS m/z 422 ([M+Na]⁺).

Example 5 Step 1: Preparation of tert-butyl((3S,7S,8R,9S)-8-butyl-7-hydroxy-9-methyl-2-oxooxonan-3-yl)carbamate(21)

To a solution of tert-butyl((3S,7S,8S,9S)-7-(benzyloxy)-8-butyl-9-methyl-2-oxooxonan-3-yl)carbamate(0.600 g, 1.38 mmol) in EtOAc (15 mL) was added 10% Pd/C (0.0740 g,0.0690 mmol). The reaction flask was placed under 1 atm. of hydrogen(balloon) and stirred vigorously for 72 h. The reaction was filteredthrough a pad of celite and the pad was washed with EtOAc. The filtratewas concentrated and the residue purified by flash chromatography (SiO₂;EtOAc/hexanes) to give the title compound as a colorless oil (0.405 g,1.18 mmol, 85%): ¹H NMR (400 MHz, CDCl₃) δ 5.11 (d, J=8.3 Hz, 1H), 4.71(dq, J=10.0, 6.4 Hz, 1H), 4.26-4.15 (m, 1H), 3.69 (ddd, J=8.7, 5.7, 2.2Hz, 1H), 2.34-2.22 (m, 1H), 1.97 (dddd, J=15.5, 10.1, 7.7, 5.2 Hz, 1H),1.87-1.76 (m, 1H), 1.75-1.53 (m, 5H), 1.52-1.46 (m, 1H), 1.44 (s, 9H),1.40-1.34 (m, 1H), 1.33 (d, J=6.3 Hz, 3H), 1.30 (d, J=7.1 Hz, 1H),1.23-1.13 (m, 2H), 1.10-1.00 (m, 1H), 0.90 (t, J=7.1 Hz, 3H); ¹³C NMR(101 MHz, CDCl₃) δ 173.03, 154.09, 79.78, 73.54, 72.41, 52.43, 48.04,34.24, 33.60, 28.31, 28.26, 27.61, 23.41, 19.21, 17.61, 13.97; ESIMS m/z407 ([M+Na+CH₃CN]⁺).

Example 5 Step 2: Preparation of(2S,3S,4S,8S)-8-((tert-butoxycarbonyl)amino)-3-butyl-2-methyl-9-oxooxonan-4-ylisobutyrate (14)

To a solution of tert-butyl((3S,7S,8R,9S)-8-butyl-7-hydroxy-9-methyl-2-oxooxonan-3-yl)carbamate(0.405 g, 1.179 mmol) in pyridine (3.4 mL) was added DMAP (0.029 g,0.236 mmol) followed by the slow addition of isobutyryl chloride (0.247ml, 2.36 mmol) at room temperature. The reaction was warmed to 50° C.and stirred for 3 h, at which point additional isobutyryl chloride(0.247 ml, 2.36 mmol) was added. The reaction was stirred at 50° C. foran additional 14 h, cooled to room temperature, quenched with sat. aq.NH₄Cl (5 ml), and extracted with EtOAc (3×10 ml). The combined organicextracts were dried over MgSO₄, filtered, and concentrated to dryness.The crude residue was purified by flash chromatography (SiO₂;EtOAc/hexanes) to give the title compound (0.274 g, 0.663 mmol, 56%) asa colorless oil: ¹H NMR (400 MHz, CDCl₃) δ 5.15 (d, J=8.3 Hz, 1H),4.91-4.84 (m, 1H), 4.79 (dq, J=10.0, 6.3 Hz, 1H), 4.27-4.16 (m, 1H),2.60-2.44 (m, 1H), 2.23 (dt, J=13.8, 7.1 Hz, 1H), 2.15-1.99 (m, 3H),1.73 (tdd, J=13.0, 7.3, 2.3 Hz, 1H), 1.57-1.46 (m, 1H), 1.44 (s, 9H),1.34 (d, J=6.4 Hz, 4H), 1.33-1.19 (m, 5H), 1.18-1.12 (m, 6H), 1.04-0.94(m, 1H), 0.87 (t, J=7.0 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 175.41,172.91, 154.98, 79.76, 74.44, 73.12, 52.42, 45.44, 34.24, 33.73, 33.32,30.88, 28.29, 27.38, 23.25, 19.19, 19.03, 18.88, 18.79, 18.02, 13.82;ESIMS m/z 436 ([M+Na]⁺).

Example 6 Steps 1 and 2: Preparation of:3-hydroxy-N-((3S,7S,8S,9S)-8-isopentyl-9-methyl-2-oxo-7-propoxyoxonan-3-yl)-4-methoxypicolinamide(31)

Step 1

To a solution of tert-butyl((3S,7S,8S,9S)-8-isopentyl-9-methyl-2-oxo-7-propoxyoxonan-3-yl)carbamate(330 mg, 0.826 mmol) in DCM (3 mL) was added a solution of HCl indioxane (2.07 mL, 8.26 mmol, 4M) under N₂ and the resulting solution wasstirred at room temperature for 2 h. The solvent was removed under astream of N₂, which afforded a white solid. This solid was trituratedwith Et₂O (3×3 mL) and the resulting powder was dried under high vacuumfor 1 h to give(3S,7S,8S,9S)-8-isopentyl-9-methyl-2-oxo-7-propoxyoxonan-3-aminiumchloride (59): ESIMS m/z 300 ([M+H]⁺).

Step 2

To the reaction flask containing the hydrochloride salt as a solution inDCM (3 mL) were added PyBop (473 mg, 0.908 mmol) and3-hydroxy-4-methoxypicolinic acid (154 mg, 0.908 mmol), followed byN-ethyl-N-isopropylpropan-2-amine (475 microliters (μL), 2.73 mmol).After 10 min, everything had solubilized and stirring was continued for3 h (turned pink). The reaction was treated with Celite® (2 scoopulatip-fulls) and the solvent was removed under reduced pressure. Theresulting adsorbed material was purified using flash columnchromatography (40 g SiO₂, 0→100% EtOAc/hexanes) to provide the titlecompound (250 mg, 0.555 mmol, 67%) as a white powder: mp: 45-49° C.; IR(thin film): 3368, 2954, 2872, 1739, 1651, 1529 cm⁻¹; ¹H NMR (400 MHz,CDCl₃) δ 12.14 (d, J=0.6 Hz, 1H), 8.48 (d, J=8.1 Hz, 1H), 7.99 (d, J=5.2Hz, 1H), 6.87 (d, J=5.3 Hz, 1H), 4.76 (dq, J=10.1, 6.3 Hz, 1H), 4.59(ddd, J=10.7, 8.2, 7.3 Hz, 1H), 3.94 (s, 3H), 3.52 (app dt, J=8.9, 6.4Hz, 1H), 3.32-3.23 (m, 1H), 3.16 (app dt, J=8.9, 6.6 Hz, 1H), 2.44-2.31(m, 1H), 2.25-2.10 (m, 1H), 1.98-1.86 (m, 1H), 1.86-1.72 (m, 1H),1.67-1.36 (m, 7H), 1.34 (d, J=6.3 Hz, 3H), 1.27-1.03 (m, 2H), 0.98-0.83(m, 10H); HRMS-ESI m/z [M+H)]⁺ calcd for: C₂₄H₃₉N₂O₆, 451.2803. found,451.2804.

Example 7 Preparation of((2-(((3S,7S,8S,9S)-8-isopentyl-9-methyl-2-oxo-7-propoxyoxonan-3-yl)carbamoyl)-4-methoxypyridin-3-yl)oxy)methylacetate (25)

To a solution of3-hydroxy-N-((3S,7S,8S,9S)-8-isopentyl-9-methyl-2-oxo-7-propoxyoxonan-3-yl)-4-methoxypicolinamide(125 mg, 0.277 mmol) and K₂CO₃ (77 mg, 0.555 mmol) in acetone (2.77 mL)was added bromomethyl acetate (54.4 μL, 0.555 mmol). The reaction wassealed, heated to 50° C., stirred at this temperature for 6 h, and thencooled to room temperature. The mixture was diluted with DCM (4 mL) andtreated with Celite® (3 scoopula tip-fulls). The solvent was removedunder reduced pressure and the resulting adsorbed material was directlyloaded onto a column and purified using flash column chromatography (24g SiO₂, 0→100% EtOAc/hexanes) to afford the title compound (112 mg,0.214 mmol, 77%) as a sticky, slightly yellow oil: IR (thin film): 3378,2954, 2872, 1740, 1677, 1504, 1202 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.31(d, J=8.1 Hz, 1H), 8.28 (d, J=5.4 Hz, 1H), 6.95 (d, J=5.4 Hz, 1H), 5.74(s, 2H), 4.74 (dq, J=10.1, 6.3 Hz, 1H), 4.61 (app dt, J=10.7, 7.6 Hz,1H), 3.91 (s, 3H), 3.52 (app dt, J=8.9, 6.4 Hz, 1H), 3.31-3.22 (m, 1H),3.15 (app dt, J=8.9, 6.6 Hz, 1H), 2.45-2.33 (m, 1H), 2.21-2.09 (m, 1H),2.07 (s, 3H), 1.98-1.86 (m, 1H), 1.85-1.70 (m, 1H), 1.67-1.28 (m, 10H),1.24-1.03 (m, 2H), 0.97-0.84 (m, 10H); HRMS-ESI m/z [M+Na]¹ calcd for:C₂₇H₄₂N₂NaO₈, 545.2833. found, 545.2853.

Example 8 Preparation of2-(((3S,7S,8S,9S)-8-isopentyl-9-methyl-2-oxo-7-propoxyoxonan-3-yl)carbamoyl)-4-methoxypyridin-3-ylacetate (74)

To a solution of3-hydroxy-N-((3S,7S,8S,9S)-8-isopentyl-9-methyl-2-oxo-7-propoxyoxonan-3-yl)-4-methoxypicolinamide(75 mg, 0.166 mmol) were added TEA (34.8 μL, 0.250 mmol) and acetylchloride (17.8 μL, 0.250 mmol) in DCM (0.832 mL). The reaction wasstirred at room temperature for 4 h and then treated with Celite® (3scoopula tip-fulls). The solvent was removed under reduced pressure andthe resulting adsorbed material was directly loaded onto a column andpurified using flash column chromatography (24 g SiO₂, 0→100%EtOAc/hexanes) to afford the title compound (74 mg, 0.150 mmol, 90%) asa white powder (hygroscopic): IR (thin film): 3383, 2953, 2871, 1772,1737, 1678, 1506, 1197, 1173 cm⁻¹; ¹H NMR (400 MHz, CDCl₃) δ 8.53 (d,J=8.2 Hz, 1H), 8.33 (d, J=5.4 Hz, 1H), 7.00 (d, J=5.4 Hz, 1H), 4.74 (dq,J=9.9, 6.3 Hz, 1H), 4.65-4.53 (m, 1H), 3.90 (s, 3H), 3.52 (app dt,J=8.9, 6.4 Hz, 1H), 3.31-3.22 (m, 1H), 3.15 (app dt, J=8.9, 6.6 Hz, 1H),2.43-2.30 (m, 4H), 2.22-2.07 (m, 1H), 1.96-1.84 (m, 1H), 1.83-1.69 (m,1H), 1.68-0.98 (m, 12H), 0.96-0.84 (m, 10H); HRMS-ESI m/z [M+H]⁺ calcdfor: C₂₆H₄₁N₂O₇, 493.2908. found 493.2936.

Example 9 Preparation of(2S,3S,4S,8S)-3-butyl-8-(3-((2-ethoxyacetoxyl)methoxy)-4-methoxypicolinamido)-2-methyl-9-oxooxonan-4-ylisobutyrate (71)

To a solution of(2S,3S,4S,8S)-3-butyl-8-(3-hydroxy-4-methoxypicolinamido)-2-methyl-9-oxooxonan-4-ylisobutyrate(45 mg, 0.097 mmol), Na₂CO₃ (20.5 mg, 0.194 mmol), and NaI (22.2 mg,0.145 mmol) in acetone (2.0 mL) was added chloromethyl 2-ethoxyacetate(22.2 mg, 0.145 mmol). The sealed reaction was warmed to 45° C. andstirred for 16 h. The reaction was cooled to room temperature andconcentrated under a stream of N₂. The resulting residue was purified byflash column chromatography (4 g SiO₂, 0→100% EtOAc/hexanes) to affordthe title compound (23.2 mg, 0.040 mmol, 41%) as a colorless oil: ¹H NMR(400 MHz, CDCl₃) δ 8.34 (d, J=8.1 Hz, 1H), 8.28 (d, J=5.4 Hz, 1H), 6.95(d, J=5.4 Hz, 1H), 5.82 (s, 2H), 4.90 (ddd, J=9.1, 5.6, 1.9 Hz, 1H),4.83 (dq, J=10.0, 6.4 Hz, 1H), 4.62 (ddd, J=10.7, 8.1, 7.1 Hz, 1H), 4.10(s, 2H), 3.90 (s, 3H), 3.59 (q, J=7.0 Hz, 2H), 2.53 (hept, J=7.0 Hz,1H), 2.36 (dt, J=13.7, 6.8 Hz, 1H), 2.21-2.03 (m, 2H), 1.87-1.76 (m,1H), 1.60-1.51 (m, 1H), 1.41-1.32 (m, 5H), 1.32-1.25 (m, 3H), 1.23 (t,J=7.0 Hz, 4H), 1.17 (dd, J=7.0, 0.8 Hz, 7H), 1.05 (ddt, J=15.9, 7.5, 2.2Hz, 1H), 0.88 (t, J=7.1 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ 176.48,172.33, 170.05, 162.94, 160.18, 145.80, 143.89, 142.32, 109.69, 89.56,74.52, 73.29, 67.80, 67.19, 56.22, 51.32, 45.49, 34.29, 32.91, 30.88,28.17, 27.45, 23.30, 19.22, 19.09, 18.94, 18.14, 15.01, 13.88; HRMS-ESIm/z [M+H]⁺ calcd for: C₂₉H₄₄N₂O₁₀, 581.3069. found 581.3073.

Example A Evaluation of Fungicidal Activity: Leaf Blotch of Wheat(Mycosphaerella graminicola; Anamorph: Septoria tritici; Bayer CodeSEPTTR)

Technical grades of materials were dissolved in acetone, which were thenmixed with nine volumes of water containing 110 ppm Triton X-100. Thefungicide solutions were applied onto wheat seedlings using an automatedbooth sprayer to run-off. All sprayed plants were allowed to air dryprior to further handling. All fungicides were evaluated using theaforementioned method for their activity vs. all target diseases. Wheatleaf blotch and brown rust activity were also evaluated using trackspray applications, in which case the fungicides were formulated as ECformulations, containing 0.1% Trycol 5941 in the spray solutions.

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50%mineral soil/50% soil-less Metro mix until the first leaf was fullyemerged, with 7-10 seedlings per pot. These plants were inoculated withan aqueous spore suspension of Septoria tritici either prior to or afterfungicide treatments. After inoculation the plants were kept in 100%relative humidity (one day in a dark dew chamber followed by two tothree days in a lighted dew chamber at 20° C.) to permit spores togerminate and infect the leaf. The plants were then transferred to agreenhouse set at 20° C. for disease to develop. When disease symptomswere fully expressed on the l^(st) leaves of untreated plants, infectionlevels were assessed on a scale of 0 to 100 percent disease severity.Percent disease control was calculated using the ratio of diseaseseverity on treated plants relative to untreated plants.

Example B Evaluation of Fungicidal Activity: Wheat Brown Rust (Pucciniatriticina; Synonym: Puccinia recondite f sp. tritici; Bayer code PUCCRT)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50%mineral soil/50% soil-less Metro mix until the first leaf was fullyemerged, with 7-10 seedlings per pot. These plants were inoculated withan aqueous spore suspension of Puccinia triticina either prior to orafter fungicide treatments. After inoculation the plants were kept in adark dew room at 22° C. with 100% relative humidity overnight to permitspores to germinate and infect the leaf. The plants were thentransferred to a greenhouse set at 24° C. for disease to develop.Fungicide formulation, application and disease assessment followed theprocedures as described in the Example A.

Example C Evaluation of Fungicidal Activity: Wheat Glume Blotch(Leptosphaeria nodorum; Bayer Code LEPTNO)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50%mineral soil/50% soil-less Metro mix until the first leaf was fullyemerged, with 7-10 seedlings per pot. These plants were inoculated withan aqueous spore suspension of Leptosphaeria nodorum 24 hr afterfungicide treatments. After inoculation the plants were kept in 100%relative humidity (one day in a dark dew chamber followed by two days ina lighted dew chamber at 20° C.) to permit spores to germinate andinfect the leaf. The plants were then transferred to a greenhouse set at20° C. for disease to develop. Fungicide formulation, application anddisease assessment followed the procedures as described in the ExampleA.

Example D Evaluation of Fungicidal Activity: Apple Scab (Venturiainaequalis; Bayer code VENTIN)

Apple seedlings (variety McIntosh) were grown in soil-less Metro mix,with one plant per pot. Seedlings with two expanding young leaves at thetop (older leaves at bottom of the plants were trimmed) were used in thetest. Plants were inoculated with a spore suspension of Venturiainaequalis 24 hr after fungicide treatment and kept in a 22° C. dewchamber with 100% RH for 48 hr, and then moved to a greenhouse set at20° C. for disease to develop. Fungicide formulation, application anddisease assessment on the sprayed leaves followed the procedures asdescribed in the Example A.

Example E Evaluation of Fungicidal Activity: Grape Powdery Mildew(Uncinula necator; Bayer Code UNCINE)

Grape seedlings (variety Carignane) were grown in soil-less Metro mix,with one plant per pot, and used in the test when approximately onemonth old. Plants were inoculated 24 hr after fungicide treatment byshaking spores from infected leaves over test plants. Plants weremaintained in a greenhouse set at 20° C. until disease was fullydeveloped. Fungicide formulation, application and disease assessment onthe sprayed leaves followed the procedures as described in the ExampleA.

Example F Evaluation of Fungicidal Activity: Powdery Mildew of Cucumber(Erysiphe cichoracearum; Bayer Code ERYSCI)

Cucumber seedlings (variety Bush Pickle) were grown in soil-less Metromix, with one plant per pot, and used in the test when 12 to 14 daysold. Plants were inoculated with a spore suspension 24 hr followingfungicide treatments. After inoculation the plants remained in thegreenhouse set at 20° C. until disease was fully expressed. Fungicideformulation, application and disease assessment on the sprayed leavesfollowed the procedures as described in the Example A.

Example G Evaluation of Fungicidal Activity: Leaf Spot of Sugar Beets(Cercospora beticola; Bayer Code CERCBE)

Sugar beet plants (variety HH88) were grown in soil-less Metro mix andtrimmed regularly to maintain a uniform plant size prior to test. Plantswere inoculated with a spore suspension 24 hr after fungicidetreatments. Inoculated plants were kept in a dew chamber at 22° C. for48 hr then incubated in a greenhouse set at 24° C. under a clear plastichood with bottom ventilation until disease symptoms were fullyexpressed. Fungicide formulation, application and disease assessment onthe sprayed leaves followed the procedures as described in the ExampleA.

Example H Evaluation of Fungicidal Activity: Asian Soybean Rust(Phakopsora pachyrhizi; Bayer Code PHAKPA)

Technical grades of materials were dissolved in acetone, which were thenmixed with nine volumes of water containing 0.011% Tween 20. Thefungicide solutions were applied onto soybean seedlings using anautomated booth sprayer to run-off. All sprayed plants were allowed toair dry prior to further handling.

Soybean plants (variety Williams 82) were grown in soil-less Metro mix,with one plant per pot. Two weeks old seedlings were used for testing.Plants were inoculated either 3 days prior to or 1 day after fungicidetreatments. Plants were incubated for 24 h in a dark dew room at 22° C.and 100% RH then transferred to a growth room at 23° C. for disease todevelop. Disease severity was assessed on the sprayed leaves.

Example I Evaluation of Fungicidal Activity: Wheat Powdery Mildew(Blumeria graminis Fsp. Tritici; Synonym: Erysiphe graminis Fsp.Tritici; Bayer Code ERYSGT)

Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50%mineral soil/50% soil-less Metro mix until the first leaf was fullyemerged, with 7-10 seedlings per pot. These plants were inoculated bydusting with infected stock plants 24 hr after fungicide treatments.After inoculation the plants were kept in a greenhouse set at 20° C. fordisease to develop. Fungicide formulation, application and diseaseassessment on the sprayed leaves followed the procedures as described inthe Example A.

Example J Evaluation of Fungicidal Activity: Barley Powdery Mildew(Blumeria graminis Fsp. Hordei; Synonym: Erysiphe graminis Fsp. Hordei;Bayer Code ERYSGH)

Barley seedlings (variety Harrington) were propagated in soil-less Metromix, with each pot having 8 to 12 plants, and used in the test whenfirst leaf was fully emerged. Test plants were inoculated by dustingwith infected stock plants 24 hr after fungicide treatments. Afterinoculation the plants were kept in a greenhouse set at 20° C. fordisease to develop. Fungicide formulation, application and diseaseassessment on the sprayed leaves followed the procedures as described inthe Example A.

Example K Evaluation of Fungicidal Activity: Barley Scald (Rhyncosporiumsecalis; Bayer code RHYNSE)

Barley seedlings (variety Harrington) were propagated in soil-less Metromix, with each pot having 8 to 12 plants, and used in the test whenfirst leaf was fully emerged. Test plants were inoculated by an aqueousspore suspension of Rhyncosporium secalis 24 hr after fungicidetreatments. After inoculation the plants were kept in a dew room at 20°C. with 100% relative humidity for 48 hr. The plants were thentransferred to a greenhouse set at 20° C. for disease to develop.Fungicide formulation, application and disease assessment on the sprayedleaves followed the procedures as described in the Example A.

Example L Evaluation of Fungicidal Activity: Rice Blast (Magnaporthegrisea; Anamorph: Pyricularia oryzae; Bayer code PYRIOR)

Rice seedlings (variety Japonica) were propagated in soil-less Metromix, with each pot having 8 to 14 plants, and used in the test when 12to 14 days old. Test plants were inoculated with an aqueous sporesuspension of Pyricularia oryzae 24 hr after fungicide treatments. Afterinoculation the plants were kept in a dew room at 22° C. with 100%relative humidity for 48 hr to permit spores to germinate and infect theleaf. The plants were then transferred to a greenhouse set at 24° C. fordisease to develop. Fungicide formulation, application and diseaseassessment on the sprayed leaves followed the procedures as described inthe Example A.

Example M Evaluation of Fungicidal Activity: Tomato Early Blight(Alternaria solani; Bayer Code ALTESO)

Tomato plants (variety Outdoor girl) were propagated in soil-less Metromix, with each pot having one plant, and used when 12 to 14 days old.Test plants were inoculated with an aqueous spore suspension ofAlternaria solani 24 hr after fungicide treatments. After inoculationthe plants were kept in 100% relative humidity (one day in a dark dewchamber followed by two to three days in a lighted dew chamber at 20°C.) to permit spores to germinate and infect the leaf. The plants werethen transferred to a growth room at 22° C. for disease to develop.Fungicide formulation, application and disease assessment on the sprayedleaves followed the procedures as described in the Example A.

Example N Evaluation of Fungicidal Activity: Cucumber Anthracnose(Glomerella lagenarium; Anamorph: Colletotrichum lagenarium; Bayer CodeCOLLLA)

Cucumber seedlings (variety Bush Pickle) were propagated in soil-lessMetro mix, with each pot having one plant, and used in the test when 12to 14 days old. Test plants were inoculated with an aqueous sporesuspension of Colletotrichum lagenarium 24 hr after fungicidetreatments. After inoculation the plants were kept in a dew room at 22°C. with 100% relative humidity for 48 hr to permit spores to germinateand infect the leaf. The plants were then transferred to a growth roomset at 22° C. for disease to develop. Fungicide formulation, applicationand disease assessment on the sprayed leaves followed the procedures asdescribed in the Example A.

TABLE 1 Compound Structure and Appearance Prepared According Cmpd. ToNo. Structure Example Appearance  1

Example 7. Sticky White Solid  2

Example 6, Step 2. White Foam  3

Example 1, Steps 1, 3, 6, 7, 8; Example 2, Step 1; Example 3, Steps 1,2, 3, 5; Example 4. Clear Oil  4

Example 5, Step 1. White Solid  5

Example 6, Step 1. White Solid  6

Example 1, Steps 1-5; Example 2, Step 3; Example 3, Steps 1-4; Example4. Colorless Oil  7

Example 7. White Foam  8

Example 6, Step 2. White Powder  9

Example 6, Step 1. White Solid 10

Example 1, Steps 1-5; Example 2, Step 1; Example 3, Steps 1- 3, 5;Example 4. Colorless Oil 11

Example 1, Steps 1, 3- 5; Example 2, Step 3; Example 3, Steps 1-4;Example 4. White Foam 12

Example 7. Clear Oil 13

Example 6, Step 2. White Solid 14

Example 5, Step 2. Colorless Oil 15

Example 7. Colorless Oil 16

Example 6, Step 1. White Powder 17

Example 8. White Powder 18

Example 1, Steps 1-5; Example 2, Step 2; Example 3, Steps 1-3, 5;Example 4. Colorless Oil 19

Example 1, Steps 1, 3- 5; Example 2, Step 1; Example 3, Steps 1-4;Example 4. Colorless Oil 20

Example 5, Step 1. Colorless Oil 21

Example 8. White Foam 22

Example 1, Steps 1, 3, 6, 7, 8; Example 2, Step 2; Example 3, Steps 1,2, 3, 5; Example 4. Clear Oil 23

Example 1, Steps 1-5; Example 2, Step 2; Example 3, Steps 1- 3, 5;Example 4. Colorless Oil 24

Example 1, Steps 1, 3- 5; Example 2, Step 2; Example 3, Steps 1-4;Example 4. Pale Yellow Oil 25

Example 7. Sticky Slightly Yellow Oil 26

Example 6, Step 2. White Solid 27

Example 1, Steps 1, 3, 6, 7, 8; Example 2, Step 3; Example 3, Steps 1,2, 3, 5; Example 4. Clear Oil 28

Example 1, Steps 1, 3- 5; Example 2, Step 3; Example 3; Steps 1-4;Example 4. Pale Yellow Oil 29

Example 6, Step 2. White Solid 30

Example 6, Step 1. White Solid 31

Example 6, Step 2. White Powder 32

Example 6, Step 2. White Solid 33

Example 7. White Foam 34

Example 6, Step 1. White Powder 35

Example 9. White Foam 36

Example 8. White Powder 37

Example 6, Step 2. White Solid 38

Example 6, Step 2. White Solid 39

Example 6, Step 1. White Solid 40

Example 7. White Powder 41

Example 1, Steps 1-5; Example 2, Step 2; Example 3, Steps 1- 3, 5;Example 4. Slight Yellow Oil 42

Example 7. White Foam 43

Example 7. White Foam 44

Example 8. Yellow Foam 45

Example 1, Steps 1, 3- 5; Example 2, Step 2; Example 3, Steps 1-3, 5;Example 4. Colorless Oil 46

Example 6, Step 1. White Solid 47

Example 6, Step 2. Clear Glass 48

Example 6, Steps 1. White Solid 49

Example 6, Step 2. White Powder 50

Example 7. Colorless Oil 51

Example 1, Steps 1-5; Example 2, Step 3; Example 3, Steps 1-4; Example4. White Powder 52

Example 7. Colorless Glass 53

Example 6, Step 1. White Solid 54

Example 6, Step 1. White Powder 55

Example 8. White Solid 56

Example 7. White Foam 57

Example 1, Steps 1-5; Example 2, Step 1; Example 3, Steps 1-3, 5;Example 4. Colorless Oil 58

Example 6, Step 2. White Powder 59

Example 6, Step 1. White Powder 60

Example 6, Steps 1, 2. White Solid 61

Example 7. White Foam 62

Example 6, Steps 1, 2. Clear Oil 63

Example 8. Yellow Oil 64

Example 6, Step 2. Clear Glass 65

Example 7. Clear Gel 66

Example 6, Step 1. White Solid 67

Example 6, Steps 1, 2. Clear Gel 68

Example 6, Step 1. White Solid 69

Example 6, Step 1. White Solid 70

Example 8. White Powder 71

Example 9. Colorless Oil 72

Example 8. Clear Gel 73

Example 7. Colorless Oil 74

Example 8. White Powder 75

Example 5, Step 2. Colorless Oil 76

Example 8. White Foam 77

Example 6, Step 1. White Solid 78

Example 6, Step 1. White Solid

TABLE 2 Analytical Data Cmpd. MP IR ¹³C or ¹⁹F No. (° C.) (cm⁻¹) MASS ¹HNMR NMR 1 — (Thin HRMS-ESI ¹H NMR (CDCl₃) δ 8.32 — Film) m/z (d, J = 8.1Hz, 1H), 8.28 3380, [M + H]⁺ (d, J = 5.4 Hz, 1H), 7.39- 2951, calcd for7.24 (m, 5H), 6.95 (d, J = 2869, C₃₁H₄₃N₂O₈, 5.4 Hz, 1H), 5.74 (s, 2H),1739, 571.3014; 4.74 (dq, J = 10.1, 6.3 Hz, 1676, found, 1H), 4.67-4.56(m, 2H), 1502, 571.3024 4.32 (d, J = 11.4 Hz, 1H), 1201 3.90 (s, 3H),3.47-3.39 (m, 1H), 2.46-2.34 (m, 1H), 2.33-2.16 (m, 1H), 2.07 (s, 3H),2.04-1.93 (m, 1H), 1.90-1.77 (m, 1H), 1.70-1.52 (m, 2H), 1.48-1.29 (m,6H), 1.12- 0.87 (m, 3H), 0.84 (app dd, J = 10.7, 6.6 Hz, 6H) 2 — —HRMS-ESI ¹H NMR (CDCl₃) δ 12.08 ¹⁹F NMR (CDCl₃) m/z (s, 1H), 8.51 (d, J= 8.1 δ-117.10 [M + H]⁺ Hz, 1H), 7.98 (d, J = 5.2 calcd for Hz, 1H),7.15 (dd, J = 8.5, C₂₇H₃₂FN₂O₇, 5.5 Hz, 2H), 6.97 (t, J = 515.2188; 8.6Hz, 2H), 6.87 (d, J = found, 5.2 Hz, 1H), 4.93-4.86 515.2188 (m, 1H),4.83 (ddd, J = 8.1, 6.0, 1.8 Hz, 1H), 4.62 (dt, J = 10.5, 7.5 Hz, 1H),3.93 (s, 3H), 2.76 (dd, J = 13.9, 5.4 Hz, 1H), 2.57- 2.41 (m, 2H), 2.36(dt, J = 13.8, 7.0 Hz, 1H), 2.23- 2.06 (m, 1H), 1.88-1.72 (m, 1H),1.69-1.53 (m, 1H), 1.48-1.38 (m, 1H), 1.36 (d, J = 6.4 Hz, 3H),1.33-1.22 (m, 1H), 1.07 (ddt, J = 16.1, 7.3, 2.1 Hz, 1H), 0.84-0.78 (m,2H), 0.77-0.71 (m, 2H) 3 — — ESIMS ¹H NMR (CDCl₃) δ 7.32- ¹³C NMR(CDCl₃) m/z 490.5 7.10 (m, 6H), 7.03 (d, J δ 172.99, 155.23, ([M + Na]⁺) 8.2 Hz, 2H), 6.70 (d, J = 139.95, 130.34, 8.5 Hz, 2H), 5.06 (d, J =129.93, 129.21, 8.1 Hz, 1H), 4.99-4.80 128.36, 126.11, (m, 1H), 4.22 (q,J = 7.9 116.27, 79.81, Hz, 1H), 4.18-4.03 (m, 79.12, 77.28, 1H), 2.98(dd, J = 14.8, 73.68, 52.44, 3.1 Hz, 1H), 2.72 (dd, J = 48.36, 35.41,14.8, 7.3 Hz, 1H), 2.61- 33.51, 29.16, 2.50 (m, 1H), 2.26 (s, 28.35,20.51, 3H), 2.23-1.99 (m, 3H), 20.32, 17.83 1.85-1.76 (m, 1H), 1.43 (s,9H), 1.35 (d, J = 6.4 Hz, 3H), 0.98-0.81 (m, 1H) 4 — — ESIMS ¹H NMR(CDCl₃) δ 7.25- ¹⁹F NMR (CDCl₃) m/z 418 7.14 (m, 2H), 6.99 (t, J =δ-116.54 ([M + Na]⁺ ) 8.6 Hz, 2H), 5.07 (d, J = 8.3 Hz, 1H), 4.75 (dq, J= 9.8, 6.4 Hz, 1H), 4.19 (dt, J = 10.6, 7.5 Hz, 1H), 3.64 (dd, J = 8.3,5.0 Hz, 1H), 2.88-2.64 (m, 2H), 2.25 (dt, J = 14.1, 7.5 Hz, 1H), 2.17(ddt, J = 9.8, 8.4, 6.3 Hz, 1H), 1.99- 1.86 (m, 1H), 1.78-1.67 (m, 1H),1.67-1.55 (m, 1H), 1.43 (s, 9H), 1.35 (d, J = 4.3 Hz, 1H), 1.31 (d, J =6.4 Hz, 3H), 1.28-1.13 (m, 1H), 1.11-1.00 (m, 1H) 5 — — ESIMS — — m/z338 ([M + H]⁺) 6 — — ESIMS ¹H NMR (CDCl₃) δ 7.37- ¹³C NMR (CDCl₃) m/z334 7.26 (m, 5H), 5.06 (d, J = 173.10, 154.94, ([M-Boc + H]⁺) 8.3 Hz,1H), 4.69 (dq, J = 138.40, 128.35, 9.8, 6.3 Hz, 1H), 4.60 127.99,127.63, (d, J = 11.5 Hz, 1H), 4.30 79.74, 78.84, (d, J = 11.5 Hz, 1H),4.19 73.49, 70.34, (dt, J = 10.0, 7.4 Hz, 1H), 52.45, 46.47, 3.39 (ddd,J = 8.8, 5.3, 1.6 33.59, 28.62, Hz, 1H), 2.33-2.14 (m, 28.34, 28.17,2H), 1.99-1.87 (m, 1H), 27.31, 23.39, 1.75 (td, J = 13.3, 8.0 Hz, 19.25,17.83, 13.94 1H), 1.56 (dddd, J = 18.2, 11.1, 5.5, 3.1 Hz, 3H), 1.44 (s,9H), 1.42-1.33 (m, 1H), 1.30 (d, J = 6.4 Hz, 3H), 1.24-1.14 (m, 3H),1.15-1.03 (m, 2H), 0.84 (t, J = 7.2 Hz, 3H) 7 — — HRMS-ESI ¹H NMR(CDCl₃) δ 8.33- ¹⁹F NMR (CDCl₃) m/z (d, J = 8.0 Hz, 1H), 8.27 δ-117.66[M + H]⁺ (d, J = 5.3 Hz, 1H), 7.19 calcd for (dd, J = 8.5, 5.5 Hz, 2H),C₂₉H₃₈FN₂O₈, 6.99-6.94 (m, 3H), 5.74 561.2607; (s, 2H), 4.81 (dq, J =9.8, found, 6.4 Hz, 1H), 4.60 (dt, J = 561.2615 10.7, 7.5 Hz, 1H), 3.90(s, 3H), 3.45 (dt, J = 8.7, 6.6 Hz, 1H), 3.23-3.08 (m, 1H), 2.98 (dt, J= 8.7, 6.5 Hz, 1H), 2.84 (dd, J = 14.7, 4.1 Hz, 1H), 2.63 (dd, J = 14.7,7.4 Hz, 1H), 2.39 (dt, J = 13.7, 7.1 Hz, 1H), 2.33-2.21 (m, 1H), 2.06(s, 3H), 1.81 (td, J = 13.5, 12.6, 7.8 Hz, 1H), 1.65-1.53 (m, 1H), 1.55-1.41 (m, 3H), 1.42- 1.29 (m, 1H), 1.25 (d, J = 6.5 Hz, 3H), 0.98-0.90(m, 1H), 0.88 (t, J = 7.4 Hz, 3H) 8 55-60 — HRMS-ESI ¹H NMR (CDCl₃) δ12.11- — m/z (s, 1H), 8.47 (d, J = 8.1 [M + H]⁺ Hz, 1H), 7.99 (d, J =5.2 calcd for Hz, 1H), 7.32-7.23 (m, C₂₇H₃₇N₂O₆, 2H), 6.99-6.83 (m, 4H),485.2646; 4.89 (app dq, J = 9.9, 6.3 found, Hz, 1H), 4.63 (app dt, J =485.2651 10.7, 7.7 Hz, 1H), 4.37- 4.28 (m, 1H), 3.94 (s, 3H), 2.42-2.29(m, 1H), 2.29-2.13 (m, 2H), 1.97- 1.83 (m, 1H), 1.71- 1.29 (m, 8H),1.27-1.10 (m, 2H), 1.08-0.98 (m, 1H), 0.84 (app dd, J = 13.9, 6.6 Hz,6H) 9 — — ESIMS ¹H NMR (CDCl₃) δ 8.71 — m/z 334 (bs, 3H), 7.38-7.26 (m,([M + H]⁺) 5H), 4.77-4.67 (m, 1H), 4.58 (d, J = 11.5 Hz, 1H), 4.30 (d, J= 11.5 Hz, 1H), 4.01 (t, J = 8.7 Hz, 1H), 3.38 (dd, J = 8.8, 4.8 Hz,1H), 2.61-2.49 (m, 1H), 2.25 (d, J = 15.1 Hz, 1H), 1.90 (td, J = 9.2,4.6 Hz, 1H), 1.74 (q, J = 10.9, 10.1 Hz, 2H), 1.64 (s, 1H), 1.58-1.48(m, 1H), 1.36 (dd, J = 10.5, 5.3 Hz, 1H), 1.31 (d, J = 6.3 Hz, 3H), 1.19(dh, J = 12.3, 6.4 Hz, 2H), 1.06 (dq, J = 12.0, 5.3 Hz, 2H), 0.88 (d, J= 8.1 Hz, 1H), 0.83 (t, J = 7.2 Hz, 3H) 10 — — ESIMS ¹H NMR (CDCl₃) δ7.33- ¹³C NMR (CDCl₃) m/z 442 7.21 (m, 2H), 6.99- δ 173.09, 157.74,([M + Na]⁺ ) 6.90 (m, 1H), 6.90-6.82 154.94, 129.54, (m, 2H), 5.07 (d, J= 8.2 8 121.00, 116.32, Hz, 1H), 4.83 (dq, J = 79.77, 78.50, 10.0, 6.3Hz, 1H), 4.33- 73.34, 52.45, 4.18 (m, 2H), 2.28-2.08 46.44, 33.45, (m,3H), 1.91-1.71 (m, 29.50, 28.33, 1H), 1.68-1.54 (m, 1H), 28.29, 27.75,1.52-1.46 (m, 1H), 1.44 23.23, 19.31, (s, 9H), 1.38 (d, J = 6.3 17.74,13.91 Hz, 3H), 1.33-1.20 (m, 4H), 1.19-1.05 (m, 1H), 1.01-0.91 (m, 1H),0.90- 0.79 (m, 4H) 11 — — ESIMS ¹H NMR (CDCl₃) δ 7.35- ¹⁹F NMR (CDCl₃)m/z 508 7.19 (m, 5H), 7.12 (dd, δ-117.36 ([M + Na]⁺) J = 8.5, 5.4 Hz,2H), 6.92 (t, J = 8.7 Hz, 2H), 5.09 (d, J = 8.2 Hz, 1H), 4.78 (dq, J =9.9, 6.4 Hz, 1H), 4.53 (d, J = 11.3 Hz, 1H), 4.24-4.17 (m, 1H), 4.15 (d,J = 11.2 Hz, 1H), 3.32 (ddd, J = 8.6, 5.3, 1.6 Hz, 1H), 2.84 (dd, J =15.1, 4.3 Hz, 1H), 2.61 (dd, J = 14.8, 7.4 Hz, 1H), 2.37- 2.07 (m, 3H),1.87-1.70 (m, 1H), 1.65-1.50 (m, 1H), 1.43 (s, 9H), 1.24 (d, J = 6.4 Hz,3H), 1.23- 1.11 (m, 1H), 0.99-0.83 (m, 1H) 12 — — HRMS-ESI ¹H NMR(CDCl₃) δ 8.38- — m/z 8.18 (m, 1H),7.37- [M + H]⁺ 7.10 (m, 5H), 7.04 (d,J = calcd for 8.2 Hz, 2H), 6.94 (d, J = C₃₃H₃₈N₂O₈, 4.9 Hz, 1H), 6.72(d, J = 560.2628; 8.5 Hz, 2H), 5.73 (s, 2H), found, 5.02-4.88 (m, 1H),4.62 560.2642 (d, J = 7.7 Hz, 1H), 4.18 (dd, J = 8.5, 4.3 Hz, 1H), 3.90(s, 3H), 3.01 (dd, J = 14.8, 3.3 Hz, 1H), 2.74 (dd, J = 14.8, 7.4 Hz,1H), 2.63-2.56 (m, 1H), 2.39- 2.37 (m, 1H), 2.27 (s, 3H), 2.20-2.09 (m,2H), 2.06 (s, 3H), 1.97-1.84 (m, 1H), 1.58-1.44 (m, 2H), 1.37 (d, J =6.4 Hz, 3H) 13 — (Thin ESIMS ¹H NMR (CDCl₃) δ 12.12 — Film) m/z 505 (d,J = 0.6 Hz, 1H), 8.48 3369, ([M + H]⁺) (d, J = 8.1 Hz, 1H), 7.99 2944,(d, J = 5.2 Hz, 1H), 6.87 2897, (d, J = 5.2 Hz, 1H), 4.76 1739, (dq, J =10.1, 6.3 Hz, 1H), 1641 4.59 (dt, J = 10.7, 7.7 Hz, 1H), 3.94 (s, 3H),3.61 (dt, J = 9.0, 5.9 Hz, 1H), 3.27 (ddt, J = 15.1, 9.0, 3.8 Hz, 2H),2.38 (ddd, J = 12.2, 7.5, 6.3 Hz, 1H), 2.27- 2.09 (m, 3H), 1.94-1.87 (m,1H), 1.86-1.72 (m, 3H), 1.62-1.48 (m, 2H), 1.46-1.36 (m, 2H), 1.35 (d, J= 6.3 Hz, 3H), 1.33- 1.23 (m, 4H), 1.19 (ddt, J = 16.7, 10.0, 3.8 Hz,1H), 0.91 (t, J = 7.0 Hz, 3H) 14 — — ESIMS ¹H NMR (CDCl₃) δ 5.15 ¹³C NMR(CDCl₃) m/z 436 (d, J = 8.3 Hz, 1H), 4.91- δ 175.41, 172.91, ([M + Na]⁺)4.84 (m, 1H), 4.79 (dq, J = 154.98, 79.76, 10.0, 6.3 Hz, 1H), 4.27-74.44, 73.12, 4.16 (m, 1H), 2.60- 52.42, 45.44, 2.44 (m, 1H), 2.23 (dt,J = 34.24, 33.32, 13.8, 7.1 Hz, 1H), 2.15- 30.88, 28.29, 1.99 (m, 3H),1.73 (tdd, J = 27.38, 23.25, 13.0, 7.3, 2.3 Hz, 1H), 19.19, 19.03,1.57-1.46 (m, 1H), 1.44 18.88, 18.79, (s, 9H), 1.34 (d, J = 6.4 18.02,13.82 Hz, 4H), 1.33-1.19 (m, 5H), 1.18-1.12 (m, 6H), 1.04-0.94 (m, 1H),0.87 (t, J = 7.0 Hz, 3H) 15 — (Thin HRMS-ESI ¹H NMR (CDCl₃) δ 8.31 —Film) m/z (d, J = 8.1 Hz, 1H), 8.28 3382, [M + H]⁺ (d, J = 5.4 Hz, 1H),7.38- 2938, calcd for 7.27 (m, 5H), 6.94 (d, J = 2870, C₃₀H₄₀N₂O₈, 5.4Hz, 1H), 5.74 (s, 2H), 1738, 557.2857; 4.74 (dq, J = 10.2, 6.3 Hz, 1675found, 1H), 4.66-4.57 (m, 2H), 557.2864 4.32 (d, J = 11.5 Hz, 1H), 3.91(s, 3H), 3.42 (ddd, J = 8.8, 5.3, 1.6 Hz, 1H), 2.46-2.35 (m, 1H), 2.32-2.18 (m, 1H), 2.07 (s, 3H), 1.97 (ddd, J = 13.3, 8.9, 4.6 Hz, 1H), 1.90-1.77 (m, 1H), 1.67-1.52 (m, 2H), 1.45-1.35 (m, 2H), 1.32 (d, J = 6.3 Hz,3H), 1.29-1.15 (m, 2H), 1.15-1.05 (m, 2H), 0.99- 0.88 (m, 1H), 0.84 (t,J = 7.2 Hz, 3H) 16 — — ESIMS — — m/z 348 [M + H]⁺ 17 58-62 — HRMS-ESI ¹HNMR (CDCl₃) δ 8.57- — m/z 8.50 (m, 1H), 8.33 (d, J = [M + H]⁺ 5.5 Hz,1H), 7.38-7.24 calcd for (m, 5H), 6.99 (d, J = 5.5 C₃₀H₄₁N₂O₇, Hz, 1H),4.79-4.67 (m, 541.2908; 1H), 4.66-4.54 (m, 2H), found, 4.31 (d, J = 11.5Hz, 1H), 541.2924 3.89 (s, 3H), 3.47-3.38 (m, 1H), 2.44-2.32 (m, 4H),2.32-2.17 (m, 1H), 2.03-1.91 (m, 1H), 1.88- 1.75 (m, 1H), 1.68- 1.51 (m,2H), 1.47-1.23 (m, 6H), 1.08-0.79 (m, 9H) 18 — — ESIMS ¹H NMR (CDCl₃) δ5.06 ¹³C NMR (CDCl₃) m/z 422 (d, J = 8.2 Hz, 1H), 4.70 δ 173.11, 154.94,([M + Na]⁺) (dq, J = 10.1, 6.4 Hz, 1H), 79.93, 79.70, 4.24-4.14 (m, 1H),3.50 8 73.53, 70.41, (app dt, J = 9.0, 6.4 Hz, 52.46, 46.66, 1H),3.28-3.19 (m, 1H), 34.41, 33.63, 3.13 (app dt, J = 8.8, 6.6 29.03,28.75, Hz, 1H), 2.30-2.18 (m, 28.33, 26.26, 1H), 2.11 (dddd, J = 15.6,23.30, 22.61, 10.1, 7.9, 5.2 Hz, 1H), 22.44, 19.26, 1.87 (app dq, J =13.1, 4.6 17.80, 10.88 Hz, 1H), 1.78-1.35 (m, 16H), 1.31 (d, J = 6.3 Hz,3H), 1.24-1.03 (m, 3H), 0.96-0.75 (m, 10H) 19 — — ESIMS ¹H NMR (CDCl₃) δ7.12 ¹³C NMR (CDCl₃) m/z 508 (dd, J = 8.5, 5.5 Hz, 2H), δ 172.95, 161.36([M + Na]⁺) 7.02 (d, J = 8.3 Hz, 2H), (d, J = 244.1 Hz), 6.90 (t, J =8.7 Hz, 2H), 155.15, 154.93, 6.67 (d, J = 8.2 Hz, 2H), 135.63 (d, J =3.3 5.08 (d, J = 7.8 Hz, 1H), Hz), 130.50 (d, J = 4.89 (dq, J = 9.8, 6.4Hz, 7.8 Hz), 130.39, 1H), 4.28-4.18 (m, 1H), 129.96, 116.13, 4.12 (ddd,J = 8.0, 5.7, 1.7 115.10 (d, J = 21.1 Hz, 1H), 2.90 (dd, J = Hz), 79.79,79.13, 14.9, 3.9 Hz, 1H), 2.70 73.45, 52.49, (dd, J = 14.9, 7.1 Hz, 1H),48.69, 34.77, 2.56-2.43 (m, 1H), 2.26 33.47, 29.35, (s, 3H), 2.24-2.03(m, 28.34, 20.48, 2H), 1.88-1.74 (m, 1H), 20.28, 17.92 1.52-1.45 (m,1H), 1.43 (s, 9H), 1.34 (d, J = 6.4 Hz, 3H), 1.12 (q, J = 11.8 Hz, 1H),0.97 (ddt, J = 13.2, 6.7, 2.1 Hz, 1H) 20 — — ESIMS ¹H NMR (CDCl₃) δ 5.11¹³C NMR (CDCl₃) m/z 407 (d, J = 8.3 Hz, 1H), 4.71 δ 173.03, 154.09,([M + Na + CH₃CN]⁺) (dq, J = 10.0, 6.4 Hz, 1H), 79.78, 73.54, 4.26-4.15(m, 1H), 3.69 72.41, 52.43, (ddd, J = 8.7, 5.7, 2.2 Hz, 48.04, 34.24,1H), 2.34-2.22 (m, 1H), 33.60, 28.31, 1.97 (dddd, J = 15.5, 10.1, 28.26,27.61, 7.7, 5.2 Hz, 1H), 1.87- 23.41, 19.21, 1.76 (m, 1H), 1.75-1.5317.61, 13.97 (m, 5H), 1.52-1.46 (m, 1H), 1.44 (s, 9H), 1.40- 1.34 (m,1H), 1.33 (d, J = 6.3 Hz, 3H), 1.30 (d, J = 7.1 Hz, 1H), 1.23-1.13 (m,2H), 1.10-1.00(m, 1H), 0.90 (t, J = 7.1 Hz, 3H) 21 — — HRMS-ESI ¹H NMR(CDCl₃) δ 8.51 ¹⁹F NMR (CDCl₃) m/z (d, J = 7.5 Hz, 1H), 8.32 δ-117.18[M + H]⁺ (d, J = 5.5 Hz, 1H), 7.14 calcd for (dd, J = 8.4, 5.5 Hz, 2H),C32H36FN2O7, 7.04 (d, J = 8.6 Hz, 2H), 579.2501; 6.99 (d, J = 5.5 Hz,1H), found, 6.92 (t, J = 8.7 Hz, 2H), 579.2508 6.75-6.64 (m, 2H), 4.92(dq, J = 9.7, 6.4 Hz, 1H), 4.63 (dt, J = 10.5, 7.7 Hz, 1H), 4.26-4.04(m, 1H), 3.89 (d, J = 1.7 Hz, 3H), 2.92 (dd, J = 14.8, 3.8 Hz, 1H), 2.72(dd, J = 14.8, 7.2 Hz, 1H), 2.58-2.47 (m, 1H), 2.39 (s, 3H), 2.37-2.29(m, 1H), 2.27 (s, 3H), 2.22-2.08 (m, 1H), 1.93-1.79 (m, 1H),1.57-1.42(m, 1H), 1.34 (d, J = 6.4 Hz, 3H), 1.33- 1.21 (m, 1H), 1.02(ddt, J = 16.0, 7.6, 2.1 Hz, 1H) 22 — — ESIMS ¹H NMR (CDCl₃) δ 7.22 ¹³CNMR (CDCl₃) m/z 456.4 (tt, J = 21.8, 7.2 Hz, 6H), δ 173.04, 154.93,([M + Na]⁺) 5.07 (d, J = 8.0 Hz, 1H), 140.90, 129.86, 4.87-4.70 (m, 1H),4.18 129.10, 128.27, (q, J = 7.9 Hz, 1H), 3.25 125.84, 113.68, (dd,J =8.4, 6.5 Hz, 1H), 81.16, 75.36, 3.15 (dd, J = 8.1, 4.6 Hz, 74.15, 52.47,1H), 2.93 (dd, J = 14.7, 48.77, 36.03, 3.3 Hz, 1H), 2.88-2.75 28.86,28.34, (m, 1H), 2.60 (dd, J = 22.66, 20.22, 14.7, 7.8 Hz, 1H), 2.37-19.60, 17.83 2.19 (m, 2H), 2.19-2.01 (m, 1H), 1.78-1.67 (m, 2H),1.55-1.48 (m, 1H), 1.43 (s, 9H), 1.30-1.25 (m, 1H), 1.22 (d, J = 6.4 Hz,3H), 0.87 (d, J = 7.3 Hz, 6H) 23 — — ESIMS ¹H NMR (CDCl₃) δ 5.07 ¹³C NMR(CDCl₃) m/z 420 (d, J = 7.9 Hz, 1H), 4.70 δ 173.07, 154.91, ([M + Na]⁺)(dq, J = 10.1, 6.3 Hz, 1H), 79.69, 73.56, 4.24-4.14 (m, 1H), 3.32 73.26,52.48, (dd, J = 10.0, 6.9 Hz, 1H), 46.67, 33.57, 3.27 (ddd, J = 8.8,5.4, 1.6 29.06, 28.42, Hz, 1H), 3.11 (dd, J = 28.31, 27.65, 10.0, 6.7Hz, 1H), 2.23 23.40, 19.26, (dq, J = 10.3, 5.0, 3.2 Hz, 17.88, 13.93,1H), 2.14-2.02 (m, 1H), 10.85, 3.01, 2.89 1.90 (ddt, J = 10.2, 8.8, 4.4Hz, 1H), 1.78-1.66 (m, 1H), 1.65-1.54 (m, 1H), 1.54-1.46 (m, 1H), 1.45(m, 10H), 1.37 (m, 1H), 1.31 (m, 5H), 1.23- 1.10 (m, 2H), 1.07-0.96 (m,1H), 0.90 (t, J = 7.0 Hz, 3H), 0.82 (ddt, J = 16.1, 8.1, 1.6 Hz, 1H),0.59-0.44 (m, 2H), 0.17 (qd, J = 4.8, 2.0 Hz, 2H) 24 — — ESIMS ¹H NMR(CDCl₃) δ 7.17 ¹³C NMR (CDCl₃) m/z 460 (dd, J = 8.4, 5.5 Hz, 2H), δ173.02, 161.24 ([M + Na]⁺) 6.96 (t, J = 8.7 Hz, 2H), (d, J = 243.9 Hz),5.07 (d, J = 8.1 Hz, 1H), 154.92, 136.45 (d, 4.77 (dq, J = 9.8, 6.5 Hz,J = 3.2 Hz), 130.36 1H), 4.18 (dt, J = 10.6, 7.7 (d, J = 7.7 Hz), Hz,1H), 3.43 (dt, J = 8.6, 114.98 (d,J = 21.0 6.6 Hz, 1H), 3.14 (ddd, J =Hz), 81.21, 79.75, 8.6, 5.4, 1.6 Hz, 1H), 73.90, 70.13, 3.02-2.90 (m,1H), 2.82 52.46, 48.89, (dd, J = 14.8, 4.2 Hz, 1H), 35.36, 33.60, 2.61(dd, J = 14.7, 7.4 Hz, 28.75, 28.32, 1H), 2.33-2.16 (m, 2H), 23.23,20.19, 2.17-2.02 (m, 1H), 1.72 17.87, 10.82 (td, J = 13.3, 12.8, 7.9 Hz,1H), 1.60-1.44 (m, 3H), 1.43 (s, 9H), 1.24 (d, J = 6.4 Hz, 3H),1.21-1.07 (m, 1H), 0.87 (t, J = 7.4 Hz, 3H), 0.83 (q, J = 3.6, 1.9 Hz,1H) 25 — (Thin HRMS-ESI ¹H NMR (CDCl₃) δ 8.31 — Film) m/z (d, J = 8.1Hz, 1H), 8.28 3378, ([M + Na]⁺) (d, J = 5.4 Hz, 1H), 6.95 2954, calcdfor (d, J = 5.4 Hz, 1H), 5.74 2872, C₂₇H₄₂N₂NaO₈, (s, 2H), 4.74 (dq, J =10.1, 1740, 545.2833; 6.3 Hz, 1H), 4.61 (app dt, 1677, found, J = 10.7,7.6 Hz, 1H), 1504, 545.2853 3.91 (s, 3H), 3.52 (app dt, 1202 J = 8.9,6.4 Hz, 1H), 3.31- 3.22 (m, 1H), 3.15 (app dt, J = 8.9, 6.6 Hz, 1H),2.45-2.33 (m, 1H), 2.21- 2.09 (m, 1H), 2.07 (s, 3H), 1.98-1.76 (m, 1H),1.85-1.70 (m, 1H), 1.67- 1.28 (m, 10H), 1.24- 1.03 (m, 2H), 0.97-0.84(m, 10H) 26 — — HRMS-ESI ¹H NMR (CDCl₃) δ 12.12 ¹⁹F NMR (CDCl₃) m/z (s,1H), 8.49 (d, J = 8.1 δ-117.48 ([M + Na]⁺) Hz, 1H), 7.98 (d, J = 5.2calcd for Hz, 1H), 7.21 (dd, J = 8.5, C₂₇H₃₄FN₂O₆, 5.5 Hz, 2H), 6.97 (t,J = 501.2395; 8.7 Hz, 2H), 6.86 (d, J = found, 5.2 Hz, 1H), 4.83 (dq, J= 501.2408 9.8, 6.4 Hz, 1H), 4.59 (dt, J = 10.6, 7.6 Hz, 1H), 3.93 (s,3H), 3.30-3.13 (m, 2H), 3.00 (dd, J = 9.8, 6.3 Hz, 1H), 2.85 (dd, J =14.7, 4.4 Hz, 1H), 2.67 (dd, J = 14.7, 7.3 Hz, 1H), 2.44-2.34 (m, 1H),2.34- 2.25 (m, 1H), 2.21- 2.06 (m, 1H), 1.91-1.78 (m, 1H), 1.68-1.53 (m,1H), 1.40 (q, J = 11.8 Hz, 1H), 1.28 (d, J = 6.4 Hz, 3H), 0.99-0.85 (m,2H), 0.55-0.42 (m, 2H), 0.19 0.06 (m, 2H) 27 — — ESIMS ¹H NMR (CDCl₃) δ7.34 ¹³C NMR (CDCl₃) m/z 454.4 7.10 (m, 6H), 5.08 (d, J = δ 173.03,154.93, ([M + Na]⁺) 8.0 Hz, 1H), 4.78 (dq, J = 140.62, 129.16, 12.8, 6.3Hz, 1H), 4.19 128.28, 125.88, (q, J = 7.9 Hz, 1H), 3.19 80.77, 79.73,(q, J = 9.6, 7.6 Hz, 2H), 74.06, 73.05, 3.00-2.84 (m, 2H), 2.68 52.47,48.56, (dd, J = 14.6, 7.3 Hz, 1H), 36.10, 33.58, 2.35-2.21 (m, 2H),2.17- 28.33, 20.21, 1.97 (m, 1H), 1.88- 17.95, 10.78, 3.09, 1.64 (m,1H), 1.58-1.45 2.82 (m, 1H), 1.43 (s, 9H), 1.26 (d, J = 6.3 Hz, 3H),0.93-0.81 (m, 2H), 0.52- 0.40 (m, 2H), 0.14- 0.07 (m, 2H) 28 — — ESIMS¹H NMR (CDCl₃) δ 7.19 ¹⁹F NMR (CDCl₃) m/z 472 (dd, J = 8.4, 5.6 Hz, 2H),δ-117.59 ([M + Na]⁺) 6.96 (t, J = 8.7 Hz, 2H), 5.04 (d, J = 8.2 Hz, 1H),4.76 (dq, J = 9.9, 6.4 Hz, 1H), 4.19 (q, J = 8.3 Hz, 1H), 3.23-3.11 (m,2H), 2.97 (dd, J = 9.8, 6.4 Hz, 1H), 2.82 (dd, J = 14.7, 4.5 Hz, 1H),2.65 (dd, J = 14.7, 7.2 Hz, 1H), 2.37- 2.15 (m, 2H), 2.12-1.98 (m, 1H),1.81-1.64 (m, 1H), 1.55-1.47 (m, 1H), 1.43 (s, 9H), 1.25 (d, J = 6.4 Hz,3H), 1.21-1.10 (m, 1H), 0.95-0.75 (m, 2H), 0.53-0.41 (m, 2H), 0.17-0.04(m, 2H) 29 — (Thin ESIMS ¹H NMR (CDCl₃) δ 12.11 — Film) m/z 471 (s, 1H),8.47 (d, J = 8.1 3366, [M + H]⁺ Hz, 1H), 7.98 (d, J = 5.2 2938, Hz, 1H),7.41-7.14 (m, 2871, 2H), 6.99-6.92 (m, 1H), 1737, 6.92-6.84 (m, 3H),4.88 1649 (dq, J = 10.1, 6.3 Hz, 1H), 4.63 (dt, J = 10.7, 7.7 Hz, 1H),4.32 (ddd, J = 8.6, 5.6, 1.7 Hz, 1H), 3.93 (s, 3H), 2.41-2.31 (m, 1H),2.21 (m, 2H), 1.97-1.84 (m, 1H), 1.73-1.45 (m, 3H), 1.41 (d, J = 6.3 Hz,3H), 1.39-1.30 (m, 2H), 1.26 (td, J = 7.1, 4.8 Hz, 3H), 1.03 (ddt, J =16.0, 7.8, 1.9 Hz, 1H), 0.86 (t, J = 6.9 Hz, 3H) 30 223-224 — ESIMS ¹HNMR (CDCl₃) δ 8.68 — m/z 298 (bs, 3H), 4.72 (dd, J = [M + H]⁺ 10.2, 6.1Hz, 1H), 3.99 (t, J = 8.5 Hz, 1H), 3.38- 3.24 (m, 2H), 3.10 (dd, J =10.0, 6.7 Hz, 1H), 2.59- 2.44 (m, 1H), 2.22- 2.04 (m, 1H), 1.88 (dq, J =9.1, 4.7 Hz, 1H), 1.79- 1.65 (m, 2H), 1.64-1.51 (m, 2H), 1.46-1.24 (m,7H), 1.22-1.11 (m, 1H), 1.08-0.96 (m, 1H), 0.90 (t, J = 7.0 Hz, 3H),0.82 (dd, J = 15.8, 7.6 Hz, 1H), 0.56-0.47 (m, 2H), 0.23- 0.13 (m, 2H)31 45-49 — HRMS-ESI ¹H NMR (CDCl₃) δ 12.14 — m/z (d, J = 0.6 Hz, 1H),8.48 [M + H]⁺ (d, J = 8.1 Hz, 1H), 7.99 calcd for (d, J = 5.2 Hz, 1H),6.87 C₂₄H₃₉N₂O₆, (d, J = 5.3 Hz, 1H), 4.76 451.2803; (dq, J = 10.1, 6.3Hz, 1H), found, 4.59 (ddd, J = 10.7, 8.2, 451.2804 7.3 Hz, 1H), 3.94 (s,3H), 3.52 (app dt, J = 8.9, 6.4 Hz, 1H), 3.32-3.23 (m, 1H), 3.16 (appdt, J = 8.9, 6.6 Hz, 1H), 2.44-2.31 (m, 1H), 2.25-2.10 (m, 1H),1.98-1.86 (m, 1H), 1.86-1.72(m, 1H), 1.67- 1.36 (m, 7H), 1.34 (d, J =6.3 Hz, 3H), 1.27-1.03 (m, 2H), 0.98-0.83 (m, 10H) 32 — (Thin HRMS-ESI¹H NMR (CDCl₃) δ 12.14 — Film) m/z (d, J = 0.6 Hz, 1H), 8.47 3331, [M +H]⁺ (d, J = 8.1 Hz, 1H), 7.99 3078, calcd for (d, J = 5.2 Hz, 1H), 6.862948, C₂₄H₃₆N₂O₆, (d, J = 5.3 Hz, 1H), 4.76 2868, 449.2646; (dq, J =10.1, 6.3 Hz, 1H), 1728 found, 4.59 (dt, J = 10.7, 7.7 Hz, 449.2666 1H),3.94 (s, 3H), 3.39- 3.29 (m, 2H), 3.13 (dd, J = 10.0, 6.7 Hz, 1H), 2.38(dt, J = 13.7, 7.1 Hz, 1H), 2.22-2.08 (m, 1H), 1.95 (tt, J = 9.1, 4.4Hz, 1H), 1.87-1.75 (m, 1H), 1.68- 1.52 (m, 3H), 1.47- 1.37 (m, 1H), 1.34(d, J = 6.3 Hz, 3H), 1.33-1.29 (m, 3H), 1.24-1.15 (m, 1H), 1.09- 0.99(m, 1H), 0.91 (t, J = 7.0 Hz, 3H), 0.89-0.85 (m, 1H), 0.58- 0.48 (m,2H), 0.18 (qd, J = 4.7, 1.6 Hz, 2H) 33 — (Thin HRMS-ESI ¹H NMR (CDCl₃) δ8.31 — Film) m/z (d, J = 8.1 Hz, 1H), 8.28 3377, [M + H]⁺ (d, J = 5.4Hz, 1H), 7.32- 2938, calcd for 7.23 (m, 2H), 6.98-6.92 2871, C₂₉H₃₈N₂O₈,(m, 2H), 6.91-6.87 (m, 1740, 543.2701; 2H), 5.74 (s, 2H), 4.86 1676found, (dq, J = 10.1, 6.3 Hz, 1H), 543.2706 4.65 (dt, J = 10.7, 7.6 Hz,1H), 4.31 (ddd, J = 8.7, 5.6, 1.7 Hz, 1H), 3.90 (s, 3H), 2.36 (dtd, J =13.7, 7.6, 1.3 Hz, 1H), 2.27- 2.14 (m, 2H), 2.07 (s, 3H), 1.96-1.84 (m,1H), 1.69-1.57 (m, 1H), 1.57- 1.44 (m, 2H), 1.39 (d, J = 6.3 Hz, 3H),1.37-1.17 (m, 5H), 1.03 (ddt, J = 15.9, 7.7, 1.9 Hz, 1H), 0.86 (d, J =6.9 Hz, 3H) 34 — — ESIMS — — m/z 320 [M + H]⁺ 35 — — HRMS-ESI ¹H NMR(CDCl₃) δ 8.31 ¹⁹F NMR (CDCl₃) m/z (d, J = 8.0 Hz, 1H), 8.26 δ-117.21[M + H]⁺ (d, J = 5.3 Hz, 1H), 7.15 calcd for (dd, J = 8.5, 5.5 Hz, 2H),C₃₅H₄₂FN₂O₉, 7.07-7.01 (m, 2H), 6.97- 653.2869; 6.89 (m, 3H), 6.70 (d, J= found, 8.5 Hz, 2H), 5.81 (s, 653.2876 2H), 4.93 (dq, J = 9.6, 6.4 Hz,1H), 4.63 (dt, J = 10.5, 7.6 Hz, 1H), 4.16 (ddd, J = 8.0, 5.6, 1.7 Hz,1H), 4.09 (s, 2H), 3.89 (s, 3H), 3.58 (q, J = 7.0 Hz, 2H), 2.93 (dd, J =14.8, 3.8 Hz, 1H), 2.73 (dd, J = 14.8, 7.2 Hz, 1H), 2.60- 2.47 (m, 1H),2.41- 2.30 (m, 1H), 2.27 (s, 3H), 2.26-2.10 (m, 1H), 1.97- 1.81 (m, 1H),1.60- 1.43 (m, 1H), 1.36 (d, J = 6.4 Hz, 3H), 1.32-1.27 (m, 1H), 1.22(t, J = 7.0 Hz, 3H), 1.03 (ddt, J = 15.7, 7.2, 1.9 Hz, 1H) 36 73-77 —HRMS-ESI ¹H NMR (CDCl₃) δ 8.56- — m/z 8.49 (m, 1H), 8.33 (d, J = [M +H]⁺ 5.4 Hz, 1H), 7.31-7.22 calcd for (m, 2H), 6.99 (d, J = 5.4C₂₉H₃₉N₂O₇, Hz, 1H), 6.97-6.91 (m, 527.2752; 1H), 6.91-6.84 (m, 2H),found, 4.86 (dq, J = 10.0, 6.3 Hz, 527.2757 1H), 4.64 (app dt, J = 10.6,7.7 Hz, 1H), 4.35- 4.26 (m, 1H), 3.89 (s, 3H), 2.43-2.28 (m, 4H),2.26-2.10 (m, 2H), 1.94- 1.80 (m, 1H), 1.68- 1.58 (m, 1H), 1.57-1.41 (m,3H), 1.38 (d, J = 6.3 Hz, 3H), 1.33-1.09 (m, 3H), 1.06-0.97 (m, 1H),0.83 (app dd, J = 13.9, 6.6 Hz, 6H) 37 — — HRMS-ESI ¹H NMR (CDCl₃) δ12.12 ¹⁹F NMR (CDCl₃) m/z (s, 1H), 8.49 (d, J = 8.1 δ-117.55 [M + H]⁺Hz, 1H), 8.02-7.92 (m, calcd for 1H), 7.19 (dd, J = 9.4, 4.7C₂₆H₃₄FN₂O₆, Hz, 2H), 6.97 (t, J = 7.7 489.2395; Hz, 2H), 6.86 (d, J =5.3 found, Hz, 1H), 4.89-4.75 (m, 489.2404 1H), 4.63-4.51 (m, 1H), 3.93(s, 3H), 3.45 (td, J = 8.8, 7.9, 5.5 Hz, 1H), 3.18 (dd, J = 8.6, 4.9 Hz,1H), 2.99 (td, J = 6.7, 4.4 Hz, 1H), 2.89-2.79 (m, 1H), 2.63 (dd, J =14.7, 7.8 Hz, 1H), 2.38 (dt, J = 13.8, 7.1 Hz, 1H), 2.33-2.22 (m, 1H),2.22-2.09 (m, 1H), 1.89-1.74(m, 1H), 1.67- 1.52 (m, 1H), 1.54- 1.42 (m,2H), 1.43-1.34 (m, 1H), 1.26 (d, J = 4.4 Hz, 3H), 0.98-0.92 (m, 1H),0.88 (t, J = 7.4 Hz, 3H) 38 — — HRMS-ESI ¹H NMR (CDCl₃) δ 12.08 ¹⁹F NMR(CDCl₃) m/z (d, J = 0.6 Hz, 1H), 8.45 δ-117.15 [M + H]⁺ (d, J = 8.1 Hz,1H), 7.98 calcd for (d, J = 5.2 Hz, 1H), 7.19- C₃₀H₃₄FN₂O₆, 7.10 (m,2H), 7.05 (d, J = 537.2395 8.7 Hz, 2H), 6.99-6.88 found, (m, 2H), 6.86(d, J = 5.3 537.2410 Hz, 1H), 6.70 (d, J = 8.5 Hz, 2H), 4.95 (dq, J =9.7, 6.4 Hz, 1H), 4.63 (dt, J = 10.6, 7.7 Hz, 1H), 4.17 (ddd, J = 8.7,5.5, 1.7 Hz, 1H), 3.93 (s, 3H), 2.94 (dd, J = 14.7, 4.0 Hz, 1H), 2.74(dd, J = 14.8, 7.3 Hz, 1H), 2.61-2.49 (m, 1H), 2.41-2.29 (m, 1H), 2.28(s, 3H), 2.25-2.12 (m, 1H), 1.96-1.82 (m, 1H), 1.63-1.46 (m, 2H), 1.37(d, J = 6.4 Hz, 3H), 1.04 (ddt, J = 13.6, 7.6, 2.2 Hz, 1H) 39 — — ESIMS¹H NMR (CDCl₃) δ 8.70 — m/z 314 (s, 3H), 4.92-4.85 (m, ([M + H]⁺) 1H),4.82 (dd, J = 10.1, 6.2 Hz, 1H), 4.05 (t, J = 8.5 Hz, 1H), 2.61-2.46 (m,2H), 2.23-1.98 (m, 2H), 1.71 (t, J = 10.1 Hz, 2H), 1.67-1.53 (m, 1H),1.36 (d, J = 6.3 Hz, 3H), 1.34-1.29 (m, 3H), 1.30- 1.21 (m, 3H), 1.15(dd, J = 6.9, 0.9 Hz, 6H), 1.04- 0.93 (m, 1H), 0.87 (t, J = 7.1 Hz, 3H)40 47-51 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.31 — m/z (d, J = 8.1 Hz, 1H),8.27 [M + H]⁺ (d, J = 5.4 Hz, 1H), 7.32- calcd for 7.23 (m, 2H),6.98-6.85 C₃₀H₄₁N₂O₈, (m, 4H), 5.74 (s, 2H), 557.2857; 4.87 (dq, J =10.0, 6.4 Hz, found, 1H), 4.65 (app dt, J = 557.2865 10.7, 7.6 Hz, 1H),4.36- 4.27 (m, 1H), 3.90 (s, 3H), 2.42-2.30 (m, 1H), 2.28-2.11 (m, 2H),2.07 (s, 3H), 1.96-1.83 (m, 1H), 1.69-1.37 (m, 7H), 1.35-1.09 (m, 3H),1.08 0.98 (m, 1H), 0.84 (app dd, J = 13.9, 6.6 Hz, 6H) 41 — — ESIMS ¹HNMR (CDCl₃) δ 5.07 ¹³C NMR (CDCl₃) m/z 476 (d, J = 8.2 Hz, 1H), 4.70 δ173.07, 154.94, ([M + Na]⁺) (dq, J = 10.1, 6.3 Hz, 1H), 127.27 (q, J =4.24-4.12 (m, 1H), 3.59 276.1 Hz), 80.42, (dt, J = 9.0, 5.8 Hz, 1H),79.76, 73.48, 3.24 (tt, J = 10.4, 3.8 Hz, 66.54, 52.43, 2H), 2.31-2.06(m, 4H), 46.58, 33.53, 30.83 1.82 (dddd, J = 22.2, 12.6, (q, J = 28.9Hz), 7.6, 2.9 Hz, 3H), 1.73- 28.94, 28.51, 1.63 (m, 1H), 1.59-1.4728.31, 27.79, (m, 1H), 1.44 (s, 9H), 23.34, 22.83 (q, J = 1.42-1.35 (m,1H), 1.32 2.8 Hz), 19.24, (d, J = 6.3 Hz, 3H), 1.30- 17.74, 13.91 1.25(m, 3H), 1.23-1.10 (m, 2H), 0.94-0.77 (m, 5H) 42 — — HRMS-ESI ¹H NMR(CDCl₃) δ 8.30 ¹⁹F NMR (CDCl₃) m/z (d, J = 8.0 Hz, 1H), 8.26 δ-117.21[M + H]⁺ (d, J = 5.4 Hz, 1H), 7.15 calcd for (dd, J = 8.5, 5.5 Hz, 2H),C₃₃H₃₈FN₂O₈, 7.07-7.01 (m, 2H), 6.97- 609.2607; 6.89 (m, 3H), 6.73-found, 6.66 (m, 2H), 5.73 (s, 609.2615 2H), 4.93 (dq, J = 9.7, 6.4 Hz,1H), 4.64 (dt, J = 10.5, 7.6 Hz, 1H), 4.16 (ddd, J = 8.7, 5.6, 1.8 Hz,1H), 3.89 (s, 3H), 2.93 (dd, J = 14.9, 3.8 Hz, 1H), 2.73 (dd, J = 14.8,7.2 Hz, 1H), 2.60-2.48 (m, 1H), 2.40-2.30 (m, 1H), 2.27 (s, 3H),2.23-2.10 (m, 1H), 2.06 (s, 3H), 1.95- 1.83 (m, 1H), 1.58-1.43 (m, 1H),1.36 (d, J = 6.4 Hz, 3H), 1.32-1.23 (m, 1H), 1.03 (ddt, J = 15.9, 7.6,2.1 Hz, 1H) 43 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.34 ¹⁹F NMR (CDCl₃) m/z(d, J = 8.0 Hz, 1H), 8.27 δ-117.20 [M + H]⁺ (d, J = 5.3 Hz, 1H), 7.14calcd for (dd, J = 8.5, 5.5 Hz, 2H), C₃₀H₃₆FN₂O₉, 7.01-6.91 (m, 3H),5.74 587.2399; (s, 2H), 4.93-4.77 (m, found, 2H), 4.64 (dt, J = 10.7,7.4 587.2399 Hz, 1H), 3.91 (s, 3H), 2.76 (dd, J = 14.0, 5.5 Hz, 1H),2.57-2.29 (m, 3H), 2.21-2.09 (m, 1H), 2.07 (s, 3H), 1.86-1.72 (m, 1H),1.65-1.46 (m, 1H), 1.35 (d, J = 6.3 Hz, 3H), 1.33-1.21 (m, 2H), 1.06(ddt, J = 16.3, 7.6, 2.2 Hz, 1H), 0.83-0.77 (m, 2H), 0.77-0.69 (m, 2H)44 — (Thin HRMS-ESI ¹H NMR (CDCl₃) δ 8.54 ¹³C NMR (CDCl₃) Film) m/z (d,J = 8.2 Hz, 1H), 8.34 δ 176.47, 172.23, 3385, [M + H]⁺ (d, J = 5.4 Hz,1H), 7.00 168.89, 162.42, 2938, calcd for (d, J = 5.5 Hz, 1H), 4.89159.42, 146.71, 2873, C₂₆H₃₈N₂O₈, (ddd, J = 9.0, 5.7, 1.9 Hz, 141.42,137.46, 1772, 507.2701; 1H), 4.83 (dq, J = 10.0, 109.78, 74.50, 1728found, 6.4 Hz, 1H), 4.62 (ddd, J = 73.29, 56.28, 507.2705 10.7, 8.4, 7.2Hz, 1H), 51.06, 45.47, 3.90 (s, 3H), 2.53 (hept, J = 34.28, 33.09, 7.0Hz, 1H), 2.40 (s, 30.88, 28.15, 3H), 2.37-2.30 (m, 1H), 27.44, 23.30,2.19-2.02 (m, 2H), 1.86- 20.74, 19.19, 1.66 (m, 2H), 1.63- 19.08, 18.94,1.48 (m, 1H), 1.41-1.30 18.09, 13.87 (m, 5H), 1.27 (ddt, J = 16.9, 9.5,5.5 Hz, 3H), 1.17 (s, 6H), 1.05 (ddt, J = 16.1, 7.9, 2.5 Hz, 1H), 0.88(t, J = 7.1 Hz, 3H), 0.91-0.83 (m, 1H) 45 — — ESIMS ¹H NMR (CDCl₃) δ7.31- ¹³C NMR (CDCl₃) m/z 442 7.13 (m, 5H), 5.07 (d, J = δ 173.03,154.93 ([M + Na]⁺) 8.2 Hz, 1H), 4.85-4.72 140.77, 129.11, (m, 1H),4.24-4.12 (m, 128.25, 125.85, 1H), 3.43 (app dt, J = 8.5, 81.19, 79.73,6.6 Hz, 1H), 3.16 (ddd, J = 74.09, 70.16, 8.4, 5.4, 1.6 Hz, 1H), 52.48,48.68, 3.03-2.93 (m, 1H), 2.89 36.08, 33.65, (dd, J = 14.7, 4.0 Hz, 1H),28.75, 28.33, 2.64 (dd, J = 14.7, 7.5 Hz, 23.24, 20.22, 1H), 2.34-2.19(m, 2H), 17.88, 10.84 2.18-2.05 (m, 1H), 1.80- 1.67 (m, 1H), 1.57- 1.41(m, 12H), 1.29-1.11 (m, 4H), 0.92-0.79 (m, 4H) 46 — — ESIMS — — m/z 364[M + H]⁺ 47 — (Thin ESIMS ¹H NMR (CDCl₃) δ 12.14 — Film) m/z 485 (d, J =0.6 Hz, 1H), 8.49 3368, [M + H]⁺ (d, J = 8.1 Hz, 1H), 7.99 2937, (d, J =5.2 Hz, 1H), 7.39- 2870, 7.27 (m, 5H), 6.86 (dd, J = 1736, 5.2, 0.7 Hz,1H), 4.76 1649 (dq, J = 10.1, 6.3 Hz, 1H) 4.66-4.540.1 (m, 2H), 4.32,(d, J = 11.5 Hz, 1H), 3.93 (s, 3H), 3.43 (ddd, J = 9.1, 5.4, 1.6 Hz,1H), 2.39 (ddd, J = 12.5, 7.6, 6.4 Hz, 1H), 2.26 (dddd, J = 15.7, 10.1,8.0, 5.2 Hz, 1H), 2.03-1.93 (m, 1H), 1.92-1.78 (m, 1H), 1.71- 1.51 (m,2H), 1.46- 1.36 (m, 2H), 1.33 (d, J = 6.3 Hz, 3H), 1.30-1.15 (m, 2H),1.16-1.04(m, 2H), 0.99-0.88 (m, 1H), 0.85 (t, J = 7.2 Hz, 3H) 48 196-198— ESIMS ¹H NMR (CDCl₃) δ 4.78 — m/z 395 (ddd, J = 12.7, 8.2, 4.9 ([M +CH₃CN]⁺) Hz, 1H), 3.90 (dd, J = 10.7, 7.4 Hz, 1H), 3.66 (dt, J = 9.7,5.9 Hz, 1H), 3.36-3.29 (m, 2H), 2.23 (m, 4H), 1.91-1.81 (m, 1H),1.81-1.68 (m, 3H), 1.67-1.51 (m, 2H), 1.51- 1.38 (m, 2H), 1.39- 1.28 (m,5H), 1.27-1.17 (m, 1H), 0.92 (t, J = 7.0 Hz, 3H), 0.89-0.80 (m, 2H) 4959-64 — HRMS-ESI ¹H NMR (CDCl₃) δ 12.12 — m/z (d, J = 0.6 Hz, 1H), 8.49[M + H]⁺ (d, J = 8.1 Hz, 1H), 7.99 calcd for (d, J = 5.2 Hz, 1H), 7.33-C₂₆H₃₅N₂O₆, 7.14 (m, 5H), 6.86 (d, J = 471.2490; 5.2 Hz, 1H), 4.85 (dq,J = found, 9.8, 6.4 Hz, 1H), 4.59 471.2492 (app dt, J = 10.6, 7.6 Hz,1H), 3.93 (s, 3H), 3.45 (app dt, J = 8.6, 6.5 Hz, 1H), 3.21 (ddd, J =8.7, 5.3, 1.6 Hz, 1H), 3.00 (app dt, J = 8.7, 6.6 Hz, 1H), 2.91 (dd, J =14.7, 4.0 Hz, 1H), 2.66 (dd, J = 14.7, 7.6 Hz, 1H), 2.44- 2.27 (m, 2H),2.25-2.10 (m, 1H), 1.83 (td, J = 13.0, 7.5 Hz, 1H), 1.67- 1.32 (m, 4H),1.27 (d, J = 6.4 Hz, 3H), 0.98-0.84 (m, 4H) 50 — (Thin HRMS-ESI ¹H NMR(CDCl₃) δ 8.33 — Film) m/z (d, J = 8.1 Hz, 1H), 8.28 3379, [M + H]⁺ (d,J = 5.4 Hz, 1H), 6.95 2938, calcd for (d, J = 5.4 Hz, 1H), 5.74 2873,C₂₇H₄₀N₂O₉, (s, 2H), 4.90 (ddd, J = 9.0, 1729, 537.2807; 5.6, 1.9 Hz,1H), 4.83 (dq, 1676 found, J = 10.0, 6.4 Hz, 1H), 537.2814 4.63 (ddd, J= 10.7, 8.1, 7.1 Hz, 1H), 3.91 (s, 3H), 2.54 (hept, J = 7.0 Hz, 1H),2.43-2.32 (m, 1H), 2.14-2.09 (m, 1H), 2.07 (s, 3H), 1.82 (dtd, J = 17.5,9.7, 8.7, 4.9 Hz, 1H), 1.65-1.50 (m, 1H), 1.38 (d, J = 1.8 Hz, 1H), 1.35(d, J = 6.3 Hz, 4H), 1.33-1.23 (m, 5H), 1.17 (dd, J = 6.9, 0.8 Hz, 6H),1.10-1.01 (m, 1H), 0.88 (t, J = 7.1 Hz, 3H), 0.90- 0.83 (m, 1H) 51 97-100 — ESIMS ¹H NMR (CDCl₃) δ 7.37- — m/z 470 7.23 (m, 5H), 5.12 (d,J = ([M + Na]⁺) 8.3 Hz, 1H), 4.74-4.65 (m, 1H), 4.59 (d, J = 11.5 Hz,1H), 4.30 (d, J = 11.5 Hz, 1H), 4.25-4.13 (m, 1H), 3.43-3.35 (m, 1H),2.31-2.14 (m, 2H), 2.00- 1.88 (m, 1H), 1.82- 1.68 (m, 1H), 1.63-1.50 (m,2H), 1.49-1.33 (m, 11H), 1.30 (d, J = 6.3 Hz, 3H), 1.25-1.11 (m, 1H),1.08-0.91 (m, 2H), 0.90- 0.78 (m, 7H) 52 — (Thin ESIMS ¹H NMR (CDCl₃) δ8.31 — Film) m/z 577 (d, J = 8.1 Hz, 1H), 8.28 3379, ([M + H]⁺) (d, J =5.4 Hz, 1H), 6.95 2939, (d, J = 5.4 Hz, 1H), 5.74 2873, (s, 2H), 4.74(dq, J = 10.1, 1740, 6.3 Hz, 1H), 4.61 (dt, J = 1676 10.7, 7.6 Hz, 1H),3.91 (s, 3H), 3.60 (dt, J = 9.1, 5.9 Hz, 1H), 3.32-3.20 (m, 2H), 2.39(ddd, J = 12.5, 7.6, 6.3 Hz, 1H), 2.29- 2.09 (m, 4H), 2.07 (s, 3H),1.95-1.86 (m, 1H), 1.86-1.70 (m, 3H), 1.60- 1.46 (m, 2H), 1.45- 1.37 (m,1H), 1.35 (m, 7H), 1.24-1.13 (m, 1H), 0.90 (t, J = 7.0 Hz, 3H) 53 — —ESIMS — — m/z 334.4 ([M − Cl]⁺) 54 — — ESIMS — — m/z 334 ([M + H]⁺) 5583-86 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.51 — m/z (d, J = 7.0 Hz, 1H), 8.32[M + H]⁺ (d, J = 5.4 Hz, 1H), 7.30- calcd for 7.11 (m, 5H), 7.04 (d, J =C₃₂H₃₆N₂O₇, 8.3 Hz, 2H), 6.99 (d, J = 560.2523; 5.5 Hz, 1H), 6.71 (d, J= found, 8.5 Hz, 2H), 4.94 (dq, J = 560.2523 9.9, 6.3 Hz, 1H), 4.63 (dt,J = 10.5, 7.8 Hz, 1H), 4.23-4.12 (m, 1H), 3.89 (s, 3H), 3.00 (dd, J =14.8, 3.3 Hz, 1H), 2.73 (dd, J = 14.8, 7.4 Hz, 1H), 2.63- 2.54 (m, 1H),2.39 (s, 3H), 2.37-2.29 (m, 2H), 2.27 (s, 3H), 2.19-2.11 (m, 1H),1.94-1.82 (m, 1H), 1.78-1.63 (m, 1H), 1.59-1.47 (m, 1H), 1.35 (d, J =6.4 Hz, 3H) 56 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.29 ¹³C NMR (CDCl₃) m/z(dd, J = 15.0, 6.6 Hz, 2H), δ 172.51, 170.27, [M + H]⁺ 7.36-7.12 (m,5H), 6.94 162.96, 160.26, calcd for (d, J = 5.4 Hz, 1H), 5.74 145.72,140.65, C₃₀H₃₈N₂O₈, (s, 2H), 4.91-4.73 (m, 129.17, 128.28, 554.2628;1H), 4.61 (dt, J = 10.6, 7.6 125.88, 109.56, found, Hz, 1H), 3.90 (s,3H), 89.56, 80.83, 554.2644 3.35-3.12 (m, 2H), 2.99 74.21, 73.08, (dd, J= 9.8, 6.4 Hz, 1H), 56.18, 51.39, 2.91 (dd, J = 14.6, 4.2 Hz, 48.55,36.11, 1H), 2.70 (dd, J = 14.7, 33.06, 28.72, 7.4 Hz, 1H), 2.48-2.2620.87, 20.20, (m, 2H), 2.14-2.09 (m, 18.04, 14.20, 1H), 2.07 (s, 3H),1.91- 10.78, 3.10, 2.82 1.76 (m, 1H), 1.58 (dt, J = 15.3, 7.0 Hz, 1H),1.45- 1.30 (m, 1H), 1.28 (d, J = 6.4 Hz, 3H), 0.92 (dd, J = 14.7, 7.7Hz, 2H), 0.62- 0.40 (m, 2H), 0.16-0.07 (m, 2H) 57 — — ESIMS ¹H NMR(CDCl₃) δ 7.28- ¹³C NMR (CDCl₃) m/z 456 7.24 (m, 2H), 6.98- δ 173.05,157.77, ([M + Na]⁺) 6.90 (m, 1H), 6.90-6.83 154.93, 129.51, (m, 2H),5.04 (d, J = 8.3 121.01, 116.37, Hz, 1H), 4.83 (dq, J = 9.9, 79.67,78.39, 6.4 Hz, 1H), 4.32-4.17 73.18, 52.46, (m, 2H), 2.28-2.07 (m,46.53, 34.45, 3H), 1.87-1.73 (m, 1H), 33.38, 29.62, 1.67-1.56 (m, 1H),1.52- 28.55, 28.32, 1.42 (m, 12H), 1.38 (d, 26.15, 22.54, J = 6.3 Hz,3H), 1.30- 22.41, 19.28, 17.78 1.05 (m, 3H), 1.01-0.87 (m, 1H), 0.83(app dd, J = 14.0, 6.6 Hz, 6H) 58 — (Thin HRMS-ESI ¹H NMR (CDCl₃) δ12.14 — Film) m/z (s, 1H), 8.49 (d, J = 8.1 3367, [M + H]⁺ Hz, 1H), 7.99(d, J = 5.2 2951, calcd for Hz, 1H), 7.39-7.24 (m, 2869, C₂₈H₃₉N₂O₆,5H), 6.86 (d, J = 5.2 Hz, 1736, 499.2803; 1H), 4.76 (dq, J = 10.0, 1649,found, 6.3 Hz, 1H), 4.65-4.54 1527, 499.2814 (m, 2H), 4.32 (d, J = 11.51264 Hz, 1H), 3.93 (s, 3H), 3.44 (ddd, J = 8.8, 5.2, 1.6 Hz, 1H),2.45-2.33 (m, 1H), 2.33-2.19 (m, 1H), 2.05-1.93 (m, 1H), 1.92- 1.78 (m,1H), 1.71- 1.52 (m, 2H), 1.47-1.30 (m, 6H), 1.13-0.88 (m, 3H), 0.84 (appdd, J = 10.8, 6.6 Hz, 6H) 59 — — ESIMS — — m/z 300 ([M + H]⁺) 60 68-71 —HRMS-ESI ¹H NMR (CDCl₃) δ 12.10 — m/z (s, 1H), 8.47 (d, J = 8.1 [M + H]⁺Hz, 1H), 7.97 (d, J = 5.2 calcd for Hz, 1H), 7.36-7.12 (m, C₃₀H₃₄N₂O₆,5H), 7.04 (d, J = 8.2 Hz, 518.2417; 2H), 6.84 (d, J = 5.2 Hz, found,1H), 6.72 (d, J = 8.5 Hz, 518.2417 2H), 5.03-4.89 (m, 1H), 4.62 (dt, J =10.6, 7.7 Hz, 1H), 4.24-4.14 (m, 1H), 3.91 (s, 3H), 3.01 (dd, J = 14.8,3.3 Hz, 1H), 2.74 (dd, J = 14.8, 7.5 Hz, 1H), 2.64-2.56 (m, 1H), 2.35(dt, J = 13.7, 7.1 Hz, 1H), 2.27 (s, 3H), 2.21-2.14 (m, 1H), 1.99-1.82(m, 1H), 1.53 (dq, J = 15.8, 7.9 Hz, 1H), 1.37 (d, J = 6.4 Hz, 3H),1.30-1.20 (m, 1H), 1.02 (dd, J = 15.9, 7.5 Hz, 1H) 61 — — HRMS-ESI ¹HNMR (CDCl₃) δ 8.33 ¹⁹F NMR (CDCl₃) m/z (d, J = 8.0 Hz, 1H), 8.27δ-117.58 [M + H]⁺ (d, J = 5.3 Hz, 1H), 7.21 calcd for (dd, J = 8.4, 5.5Hz, 2H), C₃₀H₃₈FN₂O₈, 7.00-6.93 (m, 3H), 5.74 573.2607; (s, 2H), 4.81(dq, J = 10.0, found, 6.4 Hz, 1H), 4.61 (dt, J = 573.2621 10.6, 7.5 Hz,1H), 3.90 (s, 3H), 3.21 (ddd, J = 9.9, 6.5, 3.3 Hz, 2H), 3.00 (dd, J =9.8, 6.3 Hz, 1H), 2.85 (dd, J = 14.7, 4.4 Hz, 1H), 2.67 (dd, J = 14.7,7.3 Hz, 1H), 2.39 (dt, J = 13.7, 7.0 Hz, 1H), 2.34-2.25 (m, 1H),2.19-2.08 (m, 1H), 2.06 (s, 3H), 1.90-1.77 (m, 1H), 1.64-1.48 (m, 1H),1.42-1.29 (m, 1H), 1.27 (d, J = 6.3 Hz, 3H), 0.99-0.81 (m, 2H), 0.53-0.42 (m, 2H), 0.20- 0.08 (m, 2H) 62 — — HRMS-ESI ¹H NMR (CDCl₃) δ 12.13¹³C NMR (CDCl₃) m/z (s, 1H), 8.49 (d, J = 8.1 δ 171.89, 168.63, [M + H]⁺Hz, 1H), 7.98 (d, J = 5.2 155.34, 148.72, calcd for Hz, 1H), 7.41-7.07(m, 140.87, 140.48, C₂₇H₃₆N₂O₆, 5H), 6.85 (d, J = 5.2 Hz, 130.44,129.10, 484.2573; 1H), 4.94-4.74 (m, 1H),6 128.30, 125.88, found, 4.58(dt, J = 10.7, 7.6 Hz, 109.45, 81.15, 484.2571 1H), 3.92 (s, 3H), 3.2775.39, 74.58, (dd, J = 8.4, 6.5 Hz, 1H), 56.06, 51.08, 3.23-3.15 (m,1H), 2.95 48.78, 36.05, (dd, J = 14.7, 3.4 Hz, 1H), 33.02, 28.87, 2.85(dd, J = 8.4, 6.3 Hz, 28.51, 20.22, 1H), 2.62 (dd, J = 14.7, 19.62,17.85 7.9 Hz, 1H), 2.44-2.27 (m, 2H), 2.25-2.09 (m, 1H), 1.88-1.70 (m,2H), 1.65-1.55 (m, 1H), 1.40 (q, J = 11.7 Hz, 1H), 1.25 (d, J = 6.4 Hz,3H), 0.99- 0.91 (m, 1H), 0.89 (dd, J = 6.7, 1.8 Hz, 6H) 63 — (ThinHRMS-ESI ¹H NMR (CDCl₃) δ 8.53 — Film) m/z (d, J = 8.4 Hz, 1H), 8.343380, [M + H]⁺ (d, J = 5.4 Hz, 1H), 7.42- 2937, calcd for 7.27 (m, 5H),7.00 (d, J = 2870, C29H39N207, 5.5 Hz, 1H), 4.73 (dq, J = 1771,527.2752; 10.2, 6.3 Hz, 1H), 4.67- 1677 found, 4.55 (m, 2H), 4.31 (d, J= 527.2758 11.5 Hz, 1H), 3.91 (s, 3H), 3.42 (dd, J = 8.6, 4.9 Hz, 1H),2.40 (s, 4H), 2.32-2.19 (m, 1H), 2.01- 1.92 (m, 1H), 1.88- 1.76 (m, 1H),1.66-1.50 (m, 3H), 1.44-1.33 (m, 1H), 1.31 (d, J = 6.3 Hz, 3H),1.28-1.16 (m, 2H), 1.14-1.04 (m, 2H), 0.97- 0.87 (m, 1H), 0.84 (t, J =7.2 Hz, 3H) 64 — (Thin ESIMS ¹H NMR (CDCl₃) δ 12.10 — Film) m/z 465 (d,J = 0.6 Hz, 1H), 8.51 3369, ([M + H]⁺) (d, J = 8.2 Hz, 1H), 7.98 2938,(d, J = 5.2 Hz, 1H), 6.88 2873, (dd, J = 5.3, 0.6 Hz, 1H), 1728,4.96-4.80 (m, 2H), 4.61 1649 (ddd, J = 10.8, 8.2, 7.1 Hz, 1H), 3.94 (s,3H), 2.54 (p, J = 7.0 Hz, 1H), 2.42-2.31 (m, 1H), 2.16- 2.04 (m, 2H),2.02- 1.77 (m, 2H), 1.67-1.52 (m, 1H), 1.49-1.39 (m, 1H), 1.37 (d, J =6.3 Hz, 3H), 1.36-1.21 (m, 5H), 1.17 (dd, J = 7.0, 0.8 Hz, 6H), 1.07(ddt, J = 16.1, 7.7, 2.3 Hz, 1H), 0.88 (t, J = 7.1 Hz, 3H) 65 — —HRMS-ESI ¹H NMR (CDCl₃) δ 8.29 ¹³C NMR (CDCl₃) m/z (dd, J = 14.8, 6.6Hz, 2H), δ 172.52, 170.28, [M + H]⁺ 7.33-7.12 (m, 5H), 6.94 162.96,160.25, calcd for (d, J = 4.9 Hz, 1H), 5.73 145.73, 140.94, C₃₀H₄₀N₂O₈,(s, 2H), 4.91-4.75 (m, 129.11, 128.27, 556.2785; 1H), 4.60 (dt, J =10.5, 7.6 125.84, 109.56, found, Hz, 1H), 3.90 (s, 3H), 89.54, 81.21,556.2801 3.27 (dd, J = 8.4, 6.6 Hz, 77.26, 75.38, 1H), 3.18 (dd, J =8.4, 4.4 74.30, 60.39, Hz, 1H), 2.95 (dd, J = 56.18, 51.41, 14.7, 3.2Hz, 1H), 2.84 48.78, 36.04, (dd, J = 8.4, 6.4 Hz, 1H), 33.13, 28.86,2.61 (dd, J = 14.7, 7.9 Hz, 28.63, 20.87, 1H), 2.43-2.29 (m, 2H), 20.21,19.60, 17.92 2.19-2.10 (m, 1H), 2.06 (s, 3H), 1.88-1.67 (m, 3H),1.62-1.57 (m, 1H), 1.35 (q, J = 11.6 Hz, 1H), 1.24 (d, J = 6.4 Hz, 3H),0.88 (dd, J = 6.7, 1.1 Hz, 6H) ¹³C NMR (CDCl₃) 6 172.52, 170.28, 162.96,160.25, 145.73, 140.94, 129.11, 128.27, 125.84, 109.56, 89.54, 81.21,77.26, 75.38, 74.30, 60.39, 56.18, 51.41, 48.78, 36.04, 33.13, 28.86,28.63, 20.87, 20.21, 19.60, 17.92 66 — — ESIMS ¹H NMR (CDCl₃) δ 7.30 ¹³CNMR m/z 320 7.22 (m, 2H), 6.95- (CD3OD) δ 171.05, ([M + H]⁺) 6.88 (m,3H), 4.97-4.89 159.10, 130.68, (m, 1H), 4.40 (ddd, J = 122.17, 117.20,8.5, 5.6, 1.7 Hz, 1H), 3.97 79.56, 76.15, (dd, J = 10.7, 7.5 Hz, 1H),52.61, 47.90, 2.26 (ttd, J = 9.8, 6.6, 5.8, 31.47, 30.48, 1.8 Hz, 2H),2.21-2.12 29.55, 29.08, (m, 1H), 1.95-1.83 (m, 24.23, 19.60, 1H),1.68-1.45 (m, 3H), 18.43, 14.22 1.42 (d, J = 6.4 Hz, 4H), 1.40-1.35 (m,1H), 1.28 (qdd, J = 9.6, 5.2, 2.0 Hz, 3H), 0.99 (ddt, J = 16.2, 7.7, 2.1Hz, 1H), 0.85 (t, J = 7.0 Hz, 3H) 67 — — HRMS-ESI ¹H NMR (CDCl₃) δ 12.13¹³C NMR m/z (s, 1H), 8.49 (d, J = 8.1 δ 171.88, 168.65, [M + H]⁺ Hz,1H), 7.98 (d, J = 5.2 155.33, 148.71, calcd for Hz, 1H), 7.36-7.10 (m,140.58, 130.42, C₂₇H₃₄N₂O₆, 5H), 6.86 (d, J = 5.2 Hz, 129.15, 128.30,482.2417; 1H), 4.95-4.73 (m, 1H), 125.92, 109.46, found, 4.59 (dt, J =10.7, 7.6 Hz, 80.76, 74.50, 482.2424 1H), 3.93 (s, 3H), 3.26- 73.09,56.06, 3.15 (m, 2H), 2.99 (dd, J 51.07, 48.55, = 9.8, 6.4 Hz, 1H), 2.9136.11, 32.93, (dd, J = 14.7, 4.2 Hz, 1H), 28.61, 20.21, 2.70 (dd, J =14.7, 7.4 Hz, 17.97, 10.78, 3.11, 1H), 2.46-2.29 (m, 2H), 2.83 2.23-2.06(m, 1H), 1.91- 1.80 (m, 1H), 1.64- 1.53 (m, 1H), 1.39 (q, J = 11.4 Hz,1H), 1.29 (d, J = 6.4 Hz, 3H), 0.92 (dd, J = 15.0, 7.8 Hz, 2H), 0.52-0.41 (m, 2H), 0.19-0.05 (m, 2H) 68 — — ESIMS — — m/z 386 ([M + H]⁺) 69 —— ESIMS — — m/z 332.4 ([M − Cl]⁺) 70 56-61 — HRMS-ESI ¹H NMR (CDCl₃) δ8.53 — m/z (d, J = 8.3 Hz, 1H), 8.33 [M + H]⁺ (d, J = 5.4 Hz, 1H), 7.32-calcd for 7.14 (m, 5H), 6.99 (d, J = C₂₈H₃₇N₂O₇, 5.5 Hz, 1H), 4.82 (dq,J = 513.2595; 9.8, 6.4 Hz, 1H), 4.59 found, (ddd, J = 10.6, 8.3, 7.2513.2601 Hz, 1H), 3.90 (s, 3H), 3.44 (app dt, J = 8.6, 6.5 Hz, 1H), 3.19(ddd, J = 8.6, 5.3, 1.6 Hz, 1H), 2.99 (app dt, J = 8.7, 6.6 Hz, 1H),2.90 (dd, J = 14.7, 4.0 Hz, 1H), 2.65 (dd, J = 14.7, 7.5 Hz, 1H), 2.43-2.25 (m, 5H), 2.22-2.07 (m, 1H), 1.86-1.73 (m, 1H), 1.63-1.40 (m, 3H),1.40-1.21 (m, 4H), 0.98- 0.83 (m, 4H) 71 — (Thin HRMS-ESI ¹H NMR (CDCl₃)δ 8.34 — Film) m/z (d, J = 8.1 Hz, 1H), 8.28 3380, [M + H]⁺ (d, J = 5.4Hz, 1H), 6.95 2937, calcd for (d, J = 5.4 Hz, 1H), 5.82 2873,C₂₉H₄₄N₂O₁₀, (s, 2H), 4.90 (ddd, J = 9.1, 1729, 581.3069; 5.6, 1.9 Hz,1H), 4.83 (dq, 1676 found, J = 10.0, 6.4 Hz, 1H), 581.3073 4.62 (ddd, J= 10.7, 8.1, 7.1 Hz, 1H), 4.10 (s, 2H), 3.90 (s, 3H), 3.59 (q, J = 7.0Hz, 2H), 2.53 (hept, J = 7.0 Hz, 1H), 2.36 (dt, J = 13.7, 6.8 Hz, 1H),2.21- 2.03 (m, 2H), 1.87- 1.76 (m, 1H), 1.60-1.51 (m, 1H), 1.41-1.32 (m,5H), 1.32-1.25 (m, 3H), 1.23 (t, J = 7.0 Hz, 4H), 1.17 (dd, J = 7.0, 0.8Hz, 7H), 1.05 (ddt, J = 15.9, 7.5, 2.2 Hz, 1H), 0.88 (t, J = 7.1 Hz, 3H)72 — — HRMS-ESI ¹H NMR (CDCl₃) δ 8.52 ¹³C NMR (CDCl₃) m/z (d, J = 7.0Hz, 1H), 8.33 δ 172.42, 168.93, [M + H]⁺ (d, J = 5.4 Hz, 1H), 7.35-162.38, 159.43, calcd for 7.13 (m, 5H), 6.99 (d, J = 146.68, 141.54,C₂₉H₃₈N₂O₇, 5.5 Hz, 1H), 4.90-4.76 140.93, 137.47, 526.2679; (m, 1H),4.59 (dt, J = 129.12, 128.28, found, 10.6, 7.6 Hz, 1H), 3.90 (s, 125.84,109.74, 526.2693 3H), 3.26 (dd, J = 8.4, 6.5 81.21, 75.40, Hz, 1H),3.21-3.14 (m, 74.32, 56.28, 1H), 2.95 (dd, J = 14.7, 51.14, 48.78, 3.4Hz, 1H), 2.84 (dd, J = 36.04, 33.33, 8.4, 6.4 Hz, 1H), 2.61 (dd, 28.86,28.65, J = 14.7, 7.9 Hz, 1H), 20.75, 20.20, 2.39 (s, 3H), 2.37-2.2819.61, 17.89 (m, 2H), 2.20-2.10 (m, 1H), 1.84-1.51 (m, 4H), 1.39-1.26(m,1H), 1.22 (d, J = 6.4 Hz, 3H), 0.88 (d, J = 6.7 Hz, 6H) 73 — (ThinHRMS-ESI ¹H NMR (CDCl₃) δ 8.38- — Film) m/z 8.22 (m, 2H), 6.94 (d, J =3379, [M + H]⁺ 5.4 Hz, 1H), 5.74 (s, 2937, calcd for 2H), 4.74 (dq, J =10.0, 2870, C₂₄H₃₆N₂O₆, 6.3 Hz, 1H), 4.61 (dt, J = 1738, 521.2857; 10.7,7.6 Hz, 1H), 3.91 (s, 1676 found, 3H), 3.39-3.26 (m, 2H), 521.2872 3.12(dd, J = 10.0, 6.7 Hz, 1H), 2.38 (dt, J = 13.8, 7.0 Hz, 1H), 2.19-2.09(m, 1H), 2.07 (s, 3H), 2.00- 1.90 (m, 1H), 1.86-1.73 (m, 1H), 1.68-1.49(m, 3H), 1.47-1.35 (m, 1H), 1.33 (d, J = 6.4 Hz, 3H), 1.32-1.28 (m, 3H),1.24- 1.14 (m, 1H), 1.10- 0.99 (m, 1H), 0.91 (t, J = 7.0 Hz, 3H),0.88-0.84 (m, 1H), 0.59-0.46 (m, 2H), 0.18 (qd, J = 4.6, 1.2 Hz, 2H) 7446-50 — HRMS-ESI ¹H NMR (CDCl₃) δ 8.53 — m/z (d, J = 8.2 Hz, 1H), 8.33[M + H]⁺ (d, J = 5.4 Hz, 1H), 7.00 calcd for (d, J = 5.4 Hz, 1H), 4.74C₂₆H₄₁N₂O₇, (dq, J = 9.9, 6.3 Hz, 1H), 493.2908; 4.65-4.53 (m, 1H), 3.90found, (s, 3H), 3.52 (app dt, J = 493.2936 8.9, 6.4 Hz, 1H), 3.31- 3.22(m, 1H), 3.15 (app dt, J = 8.9, 6.6 Hz, 1H), 2.43-2.30 (m, 4H), 2.22-2.07 (m, 1H), 1.96- 1.84 (m, 1H), 1.83-1.69 (m, 1H), 1.68-0.98 (m, 12H),0.96-0.84 (m, 10H) 75 — — ESIMS ¹H NMR (CDCl₃) δ 7.13 ¹⁹F NMR (CDCl₃)m/z 486 (dd, J = 8.5, 5.5 Hz, 2H), δ-117.15 [M + Na]⁺ 6.96 (t, J = 8.7Hz, 2H), 5.12 (d, J = 8.2 Hz, 1H), 4.88-4.75 (m, 2H), 4.21 (dt, J =10.9, 7.7 Hz, 1H), 2.74 (dd, J = 14.3, 5.7 Hz, 1H), 2.49 (dd, J = 14.3,7.3 Hz, 1H), 2.44-2.35 (m, 1H), 2.23 (dt, J = 13.8, 7.2 Hz, 1H), 2.17-2.01 (m, 1H), 1.78-1.64 (m, 1H), 1.57-1.46 (m, 1H), 1.43 (s, 9H), 1.33(d, J = 6.4 Hz, 3H), 1.25- 1.32 (m, 1H), 1.24-1.13 (m, 1H), 1.05-0.94(m, 1H), 0.78 (dt, J = 4.5, 2.7 Hz, 2H), 0.75-0.68 (m, 2H) 76 — —HRMS-ESI ¹H NMR (CDCl₃) δ 8.52 ¹³C NMR (CDCl₃) m/z (d, J = 6.8 Hz, 1H),8.33 δ 172.42, 168.91, [M + H]⁺ (d, J = 5.4 Hz, 1H), 7.35- 162.38,159.43, calcd for 7.12 (m, 5H), 6.99 (d, J = 146.68, 141.52, C29H36N207,5.5 Hz, 1H), 4.89-4.75 140.64, 129.18, 524.2523; (m, 1H), 4.59 (dt, J =128.29, 125.88, found, 10.6, 7.6 Hz, 1H), 3.90 (s, 109.75, 80.85,524.2534 3H), 3.32-3.11 (m, 2H), 74.23, 73.12, 2.98 (dd, J = 9.8, 6.4Hz, 56.28, 51.12, 1H), 2.90 (dd, J = 14.7, 48.55, 36.12, 4.3 Hz, 1H),2.69 (dd, J = 29.71, 28.74, 14.7, 7.3 Hz, 1H), 2.39 (s, 20.75, 20.18,3H), 2.38-2.30 (m, 1H), 18.01, 10.78, 3.12, 2.16-2.05 (m, 1H), 1.87-2.83 1.75 (m, 1H), 1.68- 1.48 (m, 2H), 1.38-1.26 (m, 1H), 1.25 (s, 3H),0.99-0.77 (m, 2H), 0.54- 0.38 (m, 2H), 0.17- 0.05 (m, 2H) 77 — — ESIMS —— m/z 350 ([M + H]⁺) 78 — — ESIMS — — m/z 368.4 ([M − Cl]⁺) *¹H NMR wererun at 400 MHz unless noted otherwise *¹³C NMR were run at 101 MHzunless noted otherwise *¹⁹F NMR were run at 376 MHz unless notedotherwise

TABLE 3 Biological Testing Rating Scale Rating Table for FungalPathogens % Control Rating >70 A ≦70 B Not Tested C

TABLE 4 Biological Activity - Disease Control in High and Low VolumeApplications PUCCRT* SEPTTR* 1DP* 3DC* 1DP* 3DC* Rate Rate Cmpd. 121.5100 121.5 100 121.5 100 121.5 100 No. g/H* ppm* g/H* ppm* g/H* ppm* g/H*ppm* 1 A C A C A C A C 2 C A C A C A C B 7 A C A C A C A C 8 C A C A C AC A 12 C C C C C C C C 13 C A C B C A C B 15 A C A C A C A C 17 A C A CA C A C 21 A C B C A C B C 25 A C A C B C A C 26 C A C A C A C B 29 C AC A C A C B 31 C A C B C B C B 32 C A C A C A C A 33 A C A C A C A C 35A C B C B C B C 36 A C B C A C A C 37 C A C A C A C B 38 C A C B C A C B40 A C A C A C A C 42 A C B C A C A C 43 A C A C A C A C 44 A C A C A CA C 47 C A C A C A C B 49 C A C A C A C A 50 A C A C A C A C 52 A C A CA C A C 55 A C A C A C B C 56 C A C A C A C A 58 C A C A C B C B 60 C AC A C A C A 61 A C A C A C A C 62 C C C C C C C C 63 A C A C A C A C 64C A C B C A C A 65 A C A C A C A C 67 C A C A C A C A 70 A A A A A A A A71 A C A C A C A C 72 A C A C A C A C 73 A C A C A C A C 74 A C A C A CA C 76 C A C A C A C A *PUCCRT—Wheat Brown Rust (Puccinia triticina)*SEPTTR—Wheat Leaf Blotch (Septoria tritici) *1DP—1 Day Protectant*3DC—3 Day Curative *g/H—Grams Per Hectare *ppm—Parts Per Million

TABLE 5 Biological Activity-Disease Control at 100 ppm Cmpd. 1DP* No.ALTESO* CERCBE* COLLLA* ERYSCI* ERYSGH* 25 A A A B A 33 A A A A A 36 A AA A A 40 A A A A A 61 B A A B B 70 A A A B B 73 B A A B A 74 A A A A B*ALTESO-Tomato Early Blight (Alternaria solani) *CERCBE-Leaf Spot ofSugar Beets (Cercospora beticola) *COLLLA-Cucumber Anthracnose(Glomerella lagenarium; Anamorph: Colletotricum lagenarium)*ERYSCI-Powdery Mildew of Cucumber (Erysiphe cichoracearum)*ERYSGH-Barley Powdery Mildew (Blumeria graminis f.sp. hordei; Synonym:Erysiphe graminis f.sp. hordei) 1DP-1 Day Protectant

TABLE 6 Biological Activity-Disease Control at 100 ppm Compound. 1DP*Number LEPTNO* PYRIOR* RHYNSE* UNCINE* VENTIN* 25 A C A A A 33 A A A A C36 A C A A B 40 A A A A A 61 A A A A C 70 A A A A A 73 A A A A C 74 A AA A A *LEPTNO-Wheat Glume Blotch (Leptosphaeria nodorum) *PYRIOR-RiceBlast (Magnaporthe grisea; Anamorph: Pyricularia oryzae) *RHYNSE-BarleyScald (Rhyncosporium secalis) *UNCINE-Grape Powdery Mildew (Uncinulanecator) *VENTIN-Apple Scab (Venturia inaequalis) *1DP-1 Day Protectant

TABLE 7 Biological Activity-Disease Control at 25 ppm Cmpd. PHAKPA* No.1DP* 3DC* 25 A B 36 A B 40 A B 70 A B 74 A B *PHAKPA-Asian Soybean Rust(Phakopsora pachyrhizi) *1DP-1 Day Protectant *3DC-3 Day Curative

What is claimed is:
 1. A composition for the control of a fungalpathogen including mixtures of at least one of the compounds of Formula1

wherein X is hydrogen or C(O)R₃; Y is hydrogen, C(O)R₃, or Q; Q is

R₁ is hydrogen, alkyl, alkenyl, aryl, alkoxy, or acyl, each optionallysubstituted with 0, 1 or multiple R₆; R₂ is hydrogen, alkyl, acyl, aryl,alkenyl, or —Si(R₅)₃, each optionally substituted with 0, 1 or multipleR₆; R₃ is alkoxy or benzyloxy, each optionally substituted with 0, 1, ormultiple R₆; R₄ is hydrogen, —C(O)R₅, or —CH₂OC(O)R₅; R₅ is alkyl,alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R₆;R₆ is hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, heteroaryl,heterocyclyl, or thioalkyl, each optionally substituted with 0, 1, ormultiple R₇; and R₇ is hydrogen, alkyl, aryl, or halo.
 2. A compositionaccording to claim 1, wherein X is hydrogen and Y is Q.
 3. A compositionaccording to claim 2, wherein R₄ is hydrogen.
 4. A composition accordingto claim 3, wherein R₁ is chosen from alkyl and aryl, each optionallysubstituted with 0, 1 or multiple R₆.
 5. A composition according toclaim 3, wherein R₂ is chosen from alkyl, aryl, and acyl, eachoptionally substituted with 0, 1 or multiple R₆.
 6. A compositionaccording to claim 3, wherein R₁ is chosen from alkyl and aryl, eachoptionally substituted with 0, 1 or multiple R₆, and R₂ is chosen fromalkyl, aryl, and acyl, each optionally substituted with 0, 1 or multipleR₆.
 7. A composition according to claim 2, wherein R₄ is —C(O)R₅ or—CH₂OC(O)R₅.
 8. A composition according to claim 7, wherein R₅ is chosenfrom alkyl and alkoxy, each optionally substituted with 0, 1, ormultiple R₆.
 9. A composition according to claim 8, wherein R₁ is chosenfrom alkyl and aryl, each optionally substituted with 0, 1 or multipleR₆.
 10. A composition according to claim 8, wherein R₂ is chosen fromalkyl, aryl, and acyl, each optionally substituted with 0, 1 or multipleR₆.
 11. A composition according to claim 8, wherein R₁ is chosen fromalkyl and aryl, each optionally substituted with 0, 1 or multiple R₆,and R₂ is chosen from alkyl, aryl, and acyl, each optionally substitutedwith 0, 1 or multiple R₆.
 12. A composition according to claim 11,wherein R₅ is chosen from —CH₃ and —CH₂OCH₂CH₃.
 13. A composition forthe control of a fungal pathogen including at least one of thecompositions of claim 6 and a phytologically acceptable carriermaterial.
 14. A composition for the control of a fungal pathogenincluding at least one of the compositions of claim 11 and aphytologically acceptable carrier material.
 15. A composition for thecontrol of a fungal pathogen including at least one of the compositionsof claim 12 and a phytologically acceptable carrier material.
 16. Acomposition for the control of a fungal pathogen including mixtures ofat least one of the compositions of claim 6 and another pesticideselected from the group consisting of fungicides, insecticides,nematocides, miticides, arthropodicides, bactericides and combinationsthereof.
 17. A composition for the control of a fungal pathogenincluding mixtures of at least one of the compositions of claim 11 andanother pesticide selected from the group consisting of fungicides,insecticides, nematocides, miticides, arthropodicides, bactericides andcombinations thereof.
 18. A composition for the control of a fungalpathogen including mixtures of at least one of the compositions of claim12 and another pesticide selected from the group consisting offungicides, insecticides, nematocides, miticides, arthropodicides,bactericides and combinations thereof.
 19. The compositions according toclaim 1 wherein the fungal pathogen is selected from the groupconsisting of: Leaf Blotch of Wheat (Mycosphaerella graminicola;anamorph: Septoria tritici), Wheat Brown Rust (Puccinia triticina),Stripe Rust (Puccinia striiformis), Scab of Apple (Venturia inaequalis),Blister Smut of Maize (Ustilago maydis), Powdery Mildew of Grapevine(Uncinula necator), Barley scald (Rhynchosporium secalis), Blast of Rice(Magnaporthe grisea), Rust of Soybean (Phakopsora pachyrhizi), GlumeBlotch of Wheat (Leptosphaeria nodorum), Powdery Mildew of Wheat(Blumeria graminis f. sp. tritici), Powdery Mildew of Barley (Blumeriagraminis f. sp. hordei), Powdery Mildew of Cucurbits (Erysiphecichoracearum), Anthracnose of Cucurbits (Glomerella lagenarium), LeafSpot of Beet (Cercospora beticola), Early Blight of Tomato (Alternariasolani), and Net Blotch of Barley (Pyrenophora teres).
 20. Thecomposition according to claim 6 wherein the fungal pathogen is selectedfrom the group consisting of: Leaf Blotch of Wheat (Septoria tritici),Wheat Brown Rust (Puccinia triticina), and Rust of Soybean (Phakopsorapachyrhizi).
 21. The composition according to claim 11 wherein thefungal pathogen is selected from the group consisting of: Leaf Blotch ofWheat (Septoria tritici), Wheat Brown Rust (Puccinia triticina), andRust of Soybean (Phakopsora pachyrhizi).
 22. The composition accordingto claim 12 wherein the fungal pathogen is selected from the groupconsisting of: Leaf Blotch of Wheat (Septoria tritici), Wheat Brown Rust(Puccinia triticina), and Rust of Soybean (Phakopsora pachyrhizi).
 23. Amethod for the control and prevention of fungal attack on a plant, themethod including the step of: applying a fungicidally effective amountof at least one of the compositions of claim 6 to at least one of theplant, an area adjacent to the plant, soil adapted to support growth ofthe plant, a root of the plant, and foliage of the plant.
 24. A methodfor the control and prevention of fungal attack on a plant, the methodincluding the step of: applying a fungicidally effective amount of atleast one of the compositions of claim 11 to at least one of the plant,an area adjacent to the plant, soil adapted to support growth of theplant, a root of the plant, and foliage of the plant.
 25. A method forthe control and prevention of fungal attack on a plant, the methodincluding the step of: applying a fungicidally effective amount of atleast one of the compositions of claim 12 to at least one of the plant,an area adjacent to the plant, soil adapted to support growth of theplant, a root of the plant, and foliage of the plant.
 26. A method forthe control and prevention of fungal attack on a plant, the methodincluding the step of: applying a fungicidally effective amount of atleast one of the compositions of claim 15 to at least one of the plant,an area adjacent to the plant, soil adapted to support growth of theplant, a root of the plant, and foliage of the plant.
 27. A method forthe control and prevention of fungal attack on a plant, the methodincluding the step of: applying a fungicidally effective amount of atleast one of the compositions of claim 18 to at least one of the plant,an area adjacent to the plant, soil adapted to support growth of theplant, a root of the plant, and foliage of the plant.